Poly acetyl amine grafted xanthan gum: Synthesis, Characterization and evaluation as Mucoadhesive Polymer

Poly acetyl amine grafted xanthan gum: Synthesis, Characterization and evaluation as Mucoadhesive Polymer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Poly acetyl amine grafted xanthan gum: Synthesis, Characterization and evaluation as Mucoadhesive Polymer Neelam Singla, Manisha Patil This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4168726/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Polyacetal amine grafted xanthan gum was synthesized by treating xanthan gum with chloroacetyl chloride which resulted in an intermediate to which ammonia was reacted. Proton NMR and IR spectrum confirmed the formation of poly-acetyl amine grafting on xanthan gum (MXG). The crystallinity of MXG was confirmed by DSC and XRD. SEM image indicates that the smooth polyhedral structure of xanthan gum changed to a rough spongy surface in MXG along with size and shape. Comparative mucoadhesion evaluation of MXG using goat buccal mucosa revealed higher ex vivo bio adhesion time as compared to xanthan gum. This improved mucoadhesion property of MXG can be attributed to the formation of attractive force between negative charge mucus and positive charged amine functionality. However, grafted polyhedral amine into xanthan gum backbone also enhanced other physiochemical properties such as viscosity, gelling property and swelling index etc. Acute oral toxicity and dermal toxicity studies reveals the safety of MXG. Therefore, this grafted polymer might be well exploited as a potential polymer for various drug delivery systems. Polyacetyl amine grafted xanthan gum Polymer modification Modified xanthan gum Mucoadhesive polymer gelling agent viscosity modifier Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 1. Introduction Polysaccharides are polymeric carbohydrate structure composed of repeating monosaccharide units joined by glycosidic bonds. It is renewable sources from microorganism, plants and animals. Due to their wide abundance in nature, biocompatibility, biodegradability, easy availability, cost-effectiveness and nontoxicity, natural polymers are preferred over synthetic polymers. 1 Therefore it is used in different fields such as food; pharmaceuticals; biomedical; cosmetic and agriculture 2 . However, polysaccharides also have some drawbacks which limits their range of applications 3 . Exo polysaccharides such as microbial gums are generally contain sugar such as fructose, mannose and glucose 4 . After dextran, xanthan gum (XG) is the second mostly used microbial polysaccharide which offers best commercial applications. In the past two decades, Xanthan gum has attracted considerable interest among these natural polymers. XG is a fermentation product of the gram -ve bacterium Xanthomonas Campestris having molecular weight ranging between 2x 10 6 to 20x 10 6 Da. 5 XG having β- 1,4-D- glucopyranose glucan backbone with pendant trisaccharide side chain attached to alternate glucose residue by α- 1,3 linkage 6 . Near about 35–40% of XG units consist of pyruvate linkage of 4 and 6 position (terminal mannose) and almost 90% units of inner mannose have acetyl group at the 0–6 position in main chain 7 . It shows polymeric characters due to the presence of glucuronic acid side chain. In an aqueous solution, it shows intermolecular and intramolecular hydrogen bonding interactions due to the presence of polar groups such as hydroxy and carboxy 8 . It exhibits high intrinsic viscosity at low concentration due to these hydrogen bonding interactions and high molecular weight 9 . This high viscosity rheology along with pH salt resistance properties are satisfactory for use as suspending agent, 10 thickening agent, food stabilizer 11 , pharmaceuticals, cosmetics 12 and drug reducer in oil drilling. 13 Although XG is very useful in its native form, however its use limits in many applications due to its drawbacks, such as improper water solubility, viscosity, uncontrolled rate of hydration, insufficient gelling and swelling, slow dissolution, inadequate mechanical and thermal stability and susceptibility to microbial contamination. Modification overcomes these limitations and improves its physicochemical properties and increase its range of use. Several studies on modifications by various techniques are described in the literature such as chemical, physical, mechanical, chemoenzymatic and cross linking 14 . The hydroxy and carboxy part of XG brings about chemical alteration such as etherification, esterification, amidation and acetylation. In etherification, carboxy methyl XG enhance drug release 15 polyvinyl alcohol XG enhanced adsorption performance 16 whereas viscosity will be enhanced by oleamidopropyl dimethyl amine XG 17 , Triisopropanolamine XG 18 , hexadecyl 19 – 20 , tetradecyl XG 21 . Ester modification also reform XG which have enormous applications such as enhanced water solubility 22 – 23 , sustained release 24 , 25 . Carboxy functional group might be the centerpiece for development of amide bond which also used in various applications such as stabilizer and thickness in pharmaceutical formulations 26 , enhance mucoadhesion 27 , 28 . The hydroxy group of XG could react to aldehyde under acidic conditions to form acetyl linkage lead to enhanced solubility and viscosity 29 . Sulfoxyamine XG also enhanced viscosity, gelling and mucoadhesion and used in ophthalmic drug delivery system 30 , 31 . Physical and mechanical modification such as dry heating, annealing, moisture and heat treatment also changes physicochemical properties and increase its applications 32 – 35 . In the present investigation, we have modified XG employing chloro acetyl chloride and ammonia. The acetyl amine modified XG was characterized by FTIR, NMR, DSC, XRD and SEM. The modified physical balance method was used for the determination of mucoadhesive characteristics using goat buccal mucosa as a model membrane while other physiochemical properties such as viscosity, gelling and swelling behavior also determined along with acute oral and dermal toxicity. 2. Material & Methods All ingredients were purchased from regional distributors and from LOBA Chemie Pvt. Ltd, Mumbai, India. Melting points were found to be uncorrected. Ethical Clearance : The protocol operated in this study regarding the use of rats as an animal model for acute oral and dermal toxicity was affirmed by the Institutional Animal Ethical Committee, GIPER, Limb, Satara. 2.1 Synthesis 36 Preparation of Chloroacetyl Xanthan gum: Chloroacetyl xanthan gum was formulated by treating 10 gm xanthan gum with 100 ml pyridine. 5 ml chloroacetyl chloride was added to above mixture slowly with stirring. Stirring was done for further 2 hours and leave the reaction mixture overnight for digestion. Filtered residue was washed using rectified spirit and dried. Preparation of acetyl amine xanthan gum : 10 gm of chloro-acetyl xanthan gum was dispersed in a flask containing in 50 ml rectified spirit. The 10 ml ammonia solution was added with shaking. After 2 hours stirring mixture was filtered and washed with rectified spirit. The solid residue was dried and used for further activity. 2.2 Characterization 2.2.1.1 Fourier transform infra- red spectroscopy: BRUKAR FT-IR alpha ATR spectrometer was used for spectral determination of MXG and XG. 2.2.1.2 Proton Nuclear Magnetic Resonance: VARIAN MERCURI YH-300 NMR Spectroscopy machine used for analysis of 1 H-NMR spectra of MXG and XG. TMS was used as Internal standard. The solvent for xanthan gum and amino acetyl xanthan gum is D 2 O. 2.2.1.3 Differential Scanning Calorimetry (DSC): Thermogram for XG and MXG were reported in 40 0 C – 300 0 C temperature range at a heating rate 10 0 C/min. 2.2.1.4 X-ray diffraction: X-ray diffractometer (Bruker AXS D8 Advance) along with copper Kα-radiation produced at35 mA and 40 K v in the differential angle range of 3-60 (2θ) were used for recording X-ray diffraction of MXG. 2.2.1.5 Scanning Electron Microscopy: XG and MXG surface morphology and shape were analyzed using scanning electron microscope. The gold coated samples were mounted on aluminum stub having double layer carbon adhesive tape. The electron micrographs were measured at10 kv accelerated voltage. 2.3 Physiochemical Evaluation 2.3.1 Evaluation of mucoadhesive strength of gel 37 : Modified physical balance method was used to evaluate comparative mucoadhesive strength of MXG gel. The goat buccal mucosa was collected from the slaughter house and cleaned to remove the underlining fat and loose tissue. The membrane was washed with distilled water and then with simulated saliva having pH 6.8 at 37 o C. On the vial with rubber closure was coated by immersing into standard and test mucoadhesive agent solution (1% w/v). One end of the vial was attached with nylon thread and provision was given to raise the weight at other end. Weight was put on at specific time intervals to separate mucous from glass plate. The time and weight required to detach from the buccal mucosa was recorded as the ex vivo bio adhesion time and detachment force respectively. The result was reported as an average of six observations. The force of adhesion was calculated as Force of adhesive= 0.00981/2 2.3.2 Viscosity 38 : Brookfield viscometer (Brookfield DV-E Vis-cometer) were used for determination of the viscosity of xanthan gum and modified xanthan gum viscosity using spindle L4 at 50 and 100rpm speeds. 2.3.3 Gelling Property 36 : Gelling property was determined as previously described method. The solution of Acetyl amine xanthan gum and xanthan gum (0.2–1%, w/v) in water were prepared in test tube and left for overnight. The consistency of gel in test tubes were examined by tilting at 90 o and categorized them as solutions, viscous solution or gels on the basis of visual inspection. 2.3.4 Gelling Capacity 36 : XG and MXG were examined for gelling capacity by incorporating a solution drop in a vial having newly prepared 2 ml mimicked tear fluid. The time required for its gelling was inspected visually. 2.3.5 Swelling Index 39 : Gravimetrically determined water uptake of modified xanthan gum. 30 mg disc (prepared by a hydraulic single punch press, diameter 5.0-mm) was fixed on a small mesh and immersing them into saliva solution (pH 6.75 at 37±0.5ºC) in a beaker, weighing of the disc at preplanned time points. Excess water from the swollen discs were evacuated before measuring, Water-uptake was calculated using following formula: Where, Wt=Disc Wt. at given time. Wo=Initial Wt. 2.3.6 Toxicological Study 2.3.6.1 Acute Oral toxicity 40 : It was performed as per OECD-423 guidelines . In brief, the healthy young adult female rats ranging between 8- 12 weeks and having 140 ± 10 gm weight were used. The temperature and the relative humidity of room where maintained at 22±3 0 C and 50% respectively. Artificial lighting with 12 hours light, 12 hours dark condition and plenty of drinking water along with laboratory diets were provided. The animals were kept for 10 days under laboratory conditions prior to begin of the study. Rats were selected randomly for the study and marked them for individual identification. Animals were fasted before dosing. The dose was decided on the basis of charts. The test substance was administered in lesser quantity for a period not more than 6 hours. Each step involved three animals. The dose level to be used as the starting dose is selected as 2000 mg/kg body weight as per flow charts of Annex 2. Animals were observed immediately after dosing during the first 30 minutes, and periodically during the first 24 hours. Special attention was given during the first 4 hours, and daily thereafter, for a total of 14 days. All observations were systematically recorded and individual records being maintained for each animal. Additional observations such as changes in skin and fur, eyes and mucous membranes, tremors, convulsions, salivation, diarrhea, lethargy and coma, and also respiratory, circulatory and behavior pattern also being recorded. Individual weights of animals were determined on the day of, or immediately prior to the administration of the test substance and at least weekly thereafter. 2.3.6.2 Acute dermal toxicity 41 : It was performed as perOECD-434guidelines . The healthy young adult female rats ranging between 8- 12 weeks and having 140 ± 10 gm weight were used. With the help of shaving or clipping fur of test animals were removed from the dorsal regionof the trunk before 24 hours of the study. While removing fur of animals, area was decided on basis of weight of individual animal. The test sample along with porous gauze dressing and non-irritating tape was applied on an area which is about 10 % of the total body surface area for 24 hours. Covering of test site was done in a manner to retain test sample and the gauze dressing, further sample was removed after exposure by using water. On the basis of chart, 2000 mg/kg fixed starting dose was decided. All animals were normally observed for 14 days. Observation of animals were done within first 30 minutes, including particular attention during the first 4 hours, and every day later on for 14 days. All observations were systematically recorded, with individual records being maintained for each animal. Additional observations such as changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern also being recorded. Individual weights of animals were determined on the day of, or immediately prior to the administration of the test substance and at least weekly thereafter. 3 Results & Discussion 3.1 Synthesis The melting point of acetyl amine xanthan gum was found to be 210 0 C whereas chloro acetyl Xanthan gum was 165–170 0 C and decomposition point of Xanthan gum was 220 0 C. This difference indicate the formation of product. 3.2 Characterization 3.2.1 Fourier transform infra- red spectroscopy: FT-IR spectral analysis of XG and MXG were recorded on a BRUKAR FT-IR alpha ATR spectrometer. Xanthan gum exhibit a wide band of absorption at 3332 cm − 1 because of OH group bonded to various degree. Peak at 2918 cm − 1 for CH aliphatic stretching was observed. The presence of absorption band at 1716 & 1602 cm − 1 can be attributed to carboxyl group stretching of alkyl ester & asymmetric stretching of carboxylate ion. C-O-C of cyclic ether and–CH of methyl exhibit absorption band at 1020 cm − 1 and 1406 cm − 1 respectively due to bending vibrations. MXG exhibit absorption band at 3250 cm − 1 due to NH 2 group. The broad shape of xanthan gum due to OH group changes into sharp spikes indicating occurrence of substitution on xanthan gums hydroxyl group. The peak at 2893 cm − 1 and 1400 cm − 1 observed due to CH stretching and alkanes bending. The peak at 1018 cm − 1 was observed due to stretching of cyclic ether. Decreased hydroxyl groups signal intensity contributed the fact that the concentration of hydroxyl functions dropping in the XG. 3.2.2 Proton Nuclear Magnetic Resonance: In the NMR spectra, peak at δ 2.038 indicate CH 3 protons of acetate part of XG. The broad peak at δ 3.55 & δ 3.90 are due to hydroxyl groups present on glucose & mannose units. The protons of glucose & mannose residues are observed at δ 4.78 ppm. In case of modified xanthan gum, the methyl protons of acetate part are found at δ 1.95. The protons of glucose & mannose residues are observed at δ 4.5. The hydroxyl groups are disappeared in a modified xanthan gum indicate substitution of acetyl amine take place on xanthan gum. The broad peak at δ 8.00 are due to the amino group whereas peaks at δ 8.5 & δ 8.9 are due to the methylene groups. 3.2.3 Differential Scanning Calorimetry (DSC): As per DSC spectrum, the thermogram of XG shows a broad endotherm at 82.47 0 C whereas MXG shows endothermic peak at 88.35 0 C. XG shows DSC curve similar to amorphous material which is presented in Fig. 4 . In case of MXG, extra endothermic peak at 220 0 C was observed which may be due to the modification. 3.2.4 X-ray diffraction: The findings of DSC study were in accordance with X-ray study results. The MXG had a typical crystalline type diffractogram with the distinctive peak appearing at 19, 30, 41 and 51 2θ . 3.2.5 Scanning Electron Microscopy: The SEM photographs of XG showed smooth surface with polyhedral arrangement while MXG exhibit spongy surface with roughness. MXG exhibiting SEM image revealed that the substitution of poly acetyl amine on xanthan gum result into alteration of shape and size of parent xanthan gum. 3.3 Physiochemical Evaluation 3.3.1 Mucoadhesion property : Modified polymer exhibited 0.0703 N adhesion force to separate 1% w/v coated plate from the mucus in 33.91 sec while xanthan gum (Plain polymer) showed 0.0133N adhesion force to separate the plate, in respond to test material towards the mucus in 16.83 second. The water weight for the detachment of modified polymer was found to be 14.33 whereas for xanthan it was 2.74. This result indicate that acetyl amine modified xanthan gum exhibits the longest detachment time, highest water weight for detachment, and requires the greatest force as compared to plain xanthan gum. Mucin or Mucous glycoprotein is the principal components of mucus and having negative charged on its surface residues. Hence ionic interactions are taken place in between negatively charged mucus with cationic primary amine group of xanthan gum leading to superior mucoadhesion property as compared to plain xanthan gum. 3.3.2 Viscosity : The viscosity of Xanthan gum was modified due to the acetyl amine grafting on Xanthan gum. XG and MXG aqueous solution exhibit pseudoplastic flow behavior. Still MXG showed increased viscosity. It was observed that the viscosity of XG & MXG was increased with higher polymeric concentration, lower speed & temperature. However enhanced viscosity of MXG might be due to contribution of cationic amine character (Acetyl amine group) to its backbone chain, resulting in minimization of coulombic repulsion and increased involvement of backbone chain resulting in improved viscosity. 3.3.2 Gelling Property & Gelling Capacity study Table 1 Comparative Gelling Property & Gelling Capacity study of Xanthan gum & Modified xanthan gum Sr. No. Parameters XG MXG 1 Gelling property (% w/v) Solution 0.2 0.2 Viscous 0.8 0.4 Gel 1.2 0.6 2 Gelling capacity of solution Less than 1 hr 1 0.6 Less than 8 hr - 0.8 More than 8 hr - 0.9 More than 12 hrs - 1 MXG exhibits two fold enhancement of gelling property in contrast to the parent XG. The 1% gel prepared by xanthan gum was spread within 1 hour in the solution; while MXG remains as it is for more than 12 hours. 3.3.3 Swelling Index : Swelling degree is a characteristic of any polymer that control drug loading as well as drug release. Swelling study were performed by monitoring the changes in weight of disc as function of time. MXG showed 0.6gm swelling weight of disc within 10 min whereas XG showed 0.3gm weight. As shown in Fig. 8 , water was absorbed by MXG at a very fast and constant rate during swelling process owing to the high hydrophilicity and capillary action of MXG surface. As per SEM image, MXG having rough and spongy surface. These interconnected pores played important role in promoting a high swelling rate and effective water retention. 3.3.4 Toxicological study: Acute Oral Toxicity Xanthan gum is generally recognized as a safe for food application because it induced low or minimal toxic effect. OECD guideline 423 was used to study acute oral toxicity of modified xanthan gum. 2000 mg/kg weight from flow chart of Annex. 2c was considered while selecting dose. At this dose level, from group, no mortality was observed in three animals of a group at this dose. No mortality specify LD 50 value of modified xanthan gum was more than 2000 mg/kg which indicates that MXG having less acute toxicity similar to xanthan gum. Acute dermal Toxicity OECD guideline 434 was also used to determine acute dermal toxicity of MXG. No mortality were observed at 2000mg/ kg dose level when gel was applied on skin of rat. There are no any changes in skin & fur, eyes observed. Other parameters such as any tremors, convulsion, salivation, diarrhea, sleep & coma were not observed in the animal. 4 Conclusion The derivatization of acetyl amine group on xanthan gum was achieved successfully by treating xanthan gum with chloro acetyl chloride in basic environment and then reacted with ammonia. The characterization of modification was confirmed by FTIR, H-NMR, DSC, XRD & SEM spectra. These spectral evidences indicate that the modification on XG was successfully achieved. Acetyl amine grafted XG showed superior physiochemical properties as compared to the plain XG. The enhancement of viscosity and mucoadhesion of MXG was observed due to cationic acetyl amino group present on backbone of XG. The result of ex vivo bio adhesion studies reveal a significant increase in mucosal detachment time as compared to plain polymer indicate the more mucoadhesion application of acetyl amine grafted polymer. MXG from gel at concentration of 0.6% whereas for XG it requires 1.2% concentration. The 1% gel of MXG remain in solution for more than 12 hours indicate that gelling capacity was also increased. The water absorption by MXG at a very fast rate due to the higher hydrophilicity and capillary action. The force of detachment of MXG was more as compared to XG indicate the more mucoadhesion property. The LD50 value of MXG was more than 2 gm/kg indicate less oral toxicity No any changes were observed after application on skin indicate safe for dermal application. Therefore this grafted polymer might be well exploited as a potential carrier for various oral as well as dermal drug delivery system in future. Declarations Conflicts of interest: The authors confirm that there are no known conflicts of interest associated with this publication. Author Contribution This work was carried out in collaboration among all authors. Author Neelam Singla designed the study. Author Manisha Patil performed the laboratory research work, wrote manuscript. All authors read and approved the final manuscript. All authors read and approved the final manuscript. References J Patel, B Maji, NS Hari Narayana Moorthy, and S Maiti, RSC Adv. , 10, 27103-27136 (2020). https://doi.org/10.1039/D0RA04366D. S Gao, Z Zhang, S Li, H Su, L Tang, Y Tan, W Yu, F Han, Int. J. Biol. Macromol. 120:729–735 (2018). https://doi.org/10.1016/j.ijbiomac.2018.08.164 MM Yahoum, S Toumi, H Tahraoui, S Lefnaoui, A Hadjsadok, A Amrane, M Kebir, J Zhang, AA Assadi and L Mouni, Sustainability , 15: 6345 (2023). https://doi.org/10.3390/su15086345. J Wang, S Nie, Trends Food Sci. Technol. 87:35–46 (2019). https://doi.org/10.1016/j.tifs.2018.02.005. F García-Ochoa , VE Santos , JA Casas and E Gómez , Biotechnol. Adv. , 18:549 —579 (2000). https://doi.org/10.1016/S0734-9750(00)00050-1 AF Dário , LMA Hortêncio , MR Sierakowski , JC Queiroz Neto and DFS Petri , Carbohydr. Polym. , 84:669 —676 (2011). https://doi.org/10.1016/j.carbpol.2010.12.047 . T Riaz, MW Iqbal, B Jiang, J Chen, Int. J. Bio , . Macromol , 186:472–489 (2021). https://doi.org/10.1016/j.ijbiomac.2021.06.196 TA Camesano and KJ Wilkinson, Biomacromolecules , 2: 1184-1191 (2001) . https://doi.org/10.1021/bm015555g H Li , W Hou and X Li , Carbohydr. Polym. , 89 :24-30 (2012). https://doi.org/10.1016/j.carbpol.2012.02.022 VB Junyaprasert and G Manwiwattanakul, Int. J. Pharm., 81-91 (2008). https://doi.org/10.1016/j.ijpharm.2007.10.018 B Katzbauer, Polym. Degrad. Stab., 81-84 (1998). https://doi.org/10.1016/S0141-3910(97)00180-8. A Palaniraj and V Jayaraman, J. Food Eng., 106:1–12 (2011), https://doi.org/10.1016/j.jfoodeng.2011.03.035. YL Yang, L Ding, J Zhang, YL Zhang, J Yao and DF Cui, J. Northwest Norm. Univ., 37: 70–72 (2001). V Rana, P Rai, Carbohydr. Polym., 83:1031 (2011). DOI: 10.1016/j.carbpol.2010.09.010 . M Ahuja, A Kumar, K Singh, Int. J. Biol. Macromol., 51: 1086-1090 ( 2012) . https://doi.org/10.1016/j.ijbiomac.2012.08.023 Q Zhang, XM Hu, MY Wu, MM Wang, YY Zhao, TT Li, Reactive and Functional Polymers , 136:34–4 (2019). https://api.semanticscholar.org/CorpusID:104369698 L Shuang, Z Hong, F Bo, L Yongjun, Q Xiaohui and Z Wen, Drilling and Completion Fluids, 34:107–116 (2017), DOI: 10.3969/j.issn.1001- 5620.2017.05.020. L Chengcheng, F Bo, L Yongjun, Q Xiaohui, Z Wen and W Liwei, Oil Fi eld Chemistry, 35:628–633 (2018). https://doi.org/10.1021/acs.energyfuels.1c02941 S Maiti, S Mukherjee and R Datta, Int. J. Biol. Macromol., 70:20–25 (2014). https://doi.org/10.1016/j.ijbiomac.2014.06.031 H Quan, Y Hu, Z Huang and D Wenmeng, J. Dispersion Sci. Technol ., 41:656–666 (2020). https://doi.org/10.1080/01932691.2019.1610425 XL Qian, WH Wu, PZ Yu and JQ Wang, J. Beijing Inst. Technol., 16:346–351 (2007). XL Qian, JZ Su, WH Wu and CM Niu, Oil fi eld Chemistry, 24:154– 157 (2007). Y Tao, R Zhang, W Xu, Z Bai, Y Zhou, S Zhao, Y Xu and DQ Yu, Food Hydrocolloids, 52:923–933 (2016), https://doi.org/10.1016/j.foodhyd.2015.09.006 M Bhatia, M Ahuja and H Mehta, C arbohydr. Polym., 131:119-124 (2015), https://doi.org/10.1016/j.carbpol.2015.05.049 B Wang, Y Han, Q Lin, H Liub, C Shen, K Nan and H Chen, J. Mater. Chem. B , 4:1853–1861 (2016), http://dx.doi.org/10.1039/C5TB02046H A Roy, S Comesse, M Grisel, N Hucher, Z Souguir and F Renou, Biomacromolecules , 15:1160–1170 (2014), https://doi.org/10.1021/bm4017034 F Laffleur and M Michalek, Int. J. Biol. Macromol, 102:1250–1256 (2017), https://doi.org/10.1016/j.ijbiomac.2017.04.123. C Menzel, M Jelkmann, F Laffleur and A Bernkop- Schn¨urch, Int. J. Pharm., 517:196–202 (2017), https://doi.org/10.1016/j.ijpharm.2016.11.055. L Su, WK Ji, WZ Lan and XQ Dong, Carbohydr. Polym., 53:497–499 (2003), https://doi.org/10.1016/S0144-8617(02)00287-4 RL Jadhav, MV Patil and SN Shaikh, International Journal of Lifescience and Pharma Research, 10:3: 20-28 (2020). https://doi.org/10.22376/ijpbs/lpr.2020.10.3.P20-28 RL Jadhav, P Beloshe, AV Yadav, MV Patil and SN Shaikh, Asian Journal of Pharmaceutics , 14(2): 236 – 246 (2020). DOI: http://dx.doi.org/10.22377/ajp.v14i2.3619 . MA Zirnsak, DV Boger and V Tirtaatmadja, J. Rheol., 43:627–650 (1999), https://doi.org/10.1122/1.551007. NM Sereno, SE Hill and JR Mitchell, Carbohydr. Res ., 342:1333–1342 (2007), https://doi.org/10.1016/j.carres.2007.03.023. TJ Foster and JR Mitchell, Physical Modification of xanthan gum, in Gums and Stabilisers for Food Industry, ed. P. A. Williams and G. O. Phillips, RSC Publishing, 77-88 (2012). DOI: 10.1039/9781849734554. JS Disha, MHA Begum, MMAK Shawan, N Khatun, S Ahmed, MS Islam, MR Karim, M. R. L. Islam, M. M. Hossain and M. A. Hasan, Res. J. Mater. Sci ., 4:13–18 (2016). RL Jadhav, AV Yadav, MV Patil, Asian Journal of Chemistry. 31(12):127-132 (2019). https://doi.org/10.14233/ajchem.2020.22300 H Mahajan, H Shaikh, S Gattani, & P Nerkar, Int J pharm Sci nanotech , 2(2): 544-50 (2009). https://doi.org/10.37285/ijpsn.2009.2.2.8 Laffleur Flavia and Michalek Martina, Int J Biol Macromol , 6;102:1250-1256 (2017). https://doi.org/10.1016/j.ijbiomac.2017.04.123 S Sudarshan, BB Sunil. Brazilian Journal of Pharmaceutical Sciences . 51:689-98 (2015). https://doi.org/10.1590/S1984-82502015000300021 OECD (2002), Test No. 423: Acute Oral toxicity - Acute Toxic Class Method , OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, https://doi.org/10.1787/9789264071001-en . OECD Guideline for testing of chemicals, Proposal for a new Draft Guideline 434: Acute Dermal toxicity. 2004; 1-13 Additional Declarations No competing interests reported. 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Modified xanthan gum\u003c/em\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4168726/v1/2b180d8584d17d1a8e52f5cc.png"},{"id":54107884,"identity":"14c62475-b7b7-436e-be77-6e34fd7f2086","added_by":"auto","created_at":"2024-04-04 17:31:40","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":156732,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eProton Nuclear Magnetic Resonance spectra of Xanthan gum \u0026amp; Modified xanthan gum.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4168726/v1/5dcdf47e946dabda5ea3f50a.png"},{"id":54107885,"identity":"0cbbe333-0b8a-4902-ba45-484fc99d16c8","added_by":"auto","created_at":"2024-04-04 17:31:40","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":63499,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eDifferential Scanning Calorimetric\u003c/em\u003e\u003cem\u003e\u003cstrong\u003e \u003c/strong\u003e\u003c/em\u003e\u003cem\u003espectra of Xanthan gum \u0026amp; Modified xanthan gum.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4168726/v1/d7da6baf9984afae8a33f1ec.png"},{"id":54108810,"identity":"350c6260-fb18-4a91-bbab-2df0a0b6c947","added_by":"auto","created_at":"2024-04-04 17:39:40","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":68493,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eX-ray diffraction spectra of Modified xanthan gum\u003c/em\u003e\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4168726/v1/a021b193540aa8c8e066d048.png"},{"id":54108812,"identity":"7531980f-3983-4900-84b1-a7a00f1c40bb","added_by":"auto","created_at":"2024-04-04 17:39:40","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":364877,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eSEM photographs of Xanthan gum \u0026amp; Modified xanthan gum\u003c/em\u003e\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-4168726/v1/9abb44334f25e9887bf2b58b.png"},{"id":54107891,"identity":"6721ba4b-6f7e-455a-a73b-1c9417bc606e","added_by":"auto","created_at":"2024-04-04 17:31:40","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":23935,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eComparative viscosity study of Xanthan gum \u0026amp; Modified xanthan gum. Illustration values are the mean of three experiments ±SD.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-4168726/v1/f881ad2725d15755e2d0d51a.png"},{"id":54107887,"identity":"8d096c67-937d-48ac-b912-1da11ec75f5f","added_by":"auto","created_at":"2024-04-04 17:31:40","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":24035,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eSwelling behavior of Xanthan gum \u0026amp; Modified xanthan gum in simulated saliva solution, Illustration values are the mean of three experiments ±SD\u003c/em\u003e\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-4168726/v1/6f94a894700ec6cb3cbd1743.png"},{"id":54107888,"identity":"41bdf441-02c4-4d18-ba40-fd3590256de8","added_by":"auto","created_at":"2024-04-04 17:31:40","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":232919,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eShear stress (in Newton) measurement of Plain polymer and Modified polymer\u003c/em\u003e\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-4168726/v1/5f9324e4670b0658b82f8d39.png"},{"id":54333117,"identity":"0b5a9047-53ae-4a6b-ae02-82b30d61ee23","added_by":"auto","created_at":"2024-04-09 02:10:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1421480,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4168726/v1/80a0bd16-15c0-4318-9480-8bc721975c12.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Poly acetyl amine grafted xanthan gum: Synthesis, Characterization and evaluation as Mucoadhesive Polymer","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003ePolysaccharides are polymeric carbohydrate structure composed of repeating monosaccharide units joined by glycosidic bonds. It is renewable sources from microorganism, plants and animals. Due to their wide abundance in nature, biocompatibility, biodegradability, easy availability, cost-effectiveness and nontoxicity, natural polymers are preferred over synthetic polymers.\u003csup\u003e1\u003c/sup\u003e Therefore it is used in different fields such as food; pharmaceuticals; biomedical; cosmetic and agriculture\u003csup\u003e2\u003c/sup\u003e. However, polysaccharides also have some drawbacks which limits their range of applications\u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eExo polysaccharides such as microbial gums are generally contain sugar such as fructose, mannose and glucose\u003csup\u003e4\u003c/sup\u003e. After dextran, xanthan gum (XG) is the second mostly used microbial polysaccharide which offers best commercial applications. In the past two decades, Xanthan gum has attracted considerable interest among these natural polymers. XG is a fermentation product of the gram -ve bacterium \u003cem\u003eXanthomonas Campestris\u003c/em\u003e having molecular weight ranging between 2x 10\u003csup\u003e6\u003c/sup\u003e to 20x 10\u003csup\u003e6\u003c/sup\u003e Da.\u003csup\u003e5\u003c/sup\u003e XG having β- 1,4-D- glucopyranose glucan backbone with pendant trisaccharide side chain attached to alternate glucose residue by α- 1,3 linkage\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Near about 35\u0026ndash;40% of XG units consist of pyruvate linkage of 4 and 6 position (terminal mannose) and almost 90% units of inner mannose have acetyl group at the 0\u0026ndash;6 position in main chain\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. It shows polymeric characters due to the presence of glucuronic acid side chain. In an aqueous solution, it shows intermolecular and intramolecular hydrogen bonding interactions due to the presence of polar groups such as hydroxy and carboxy\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. It exhibits high intrinsic viscosity at low concentration due to these hydrogen bonding interactions and high molecular weight\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. This high viscosity rheology along with pH salt resistance properties are satisfactory for use as suspending agent,\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e thickening agent, food stabilizer\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, pharmaceuticals, cosmetics\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e and drug reducer in oil drilling.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAlthough XG is very useful in its native form, however its use limits in many applications due to its drawbacks, such as improper water solubility, viscosity, uncontrolled rate of hydration, insufficient gelling and swelling, slow dissolution, inadequate mechanical and thermal stability and susceptibility to microbial contamination. Modification overcomes these limitations and improves its physicochemical properties and increase its range of use. Several studies on modifications by various techniques are described in the literature such as chemical, physical, mechanical, chemoenzymatic and cross linking\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. The hydroxy and carboxy part of XG brings about chemical alteration such as etherification, esterification, amidation and acetylation. In etherification, carboxy methyl XG enhance drug release\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e polyvinyl alcohol XG enhanced adsorption performance\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e whereas viscosity will be enhanced by oleamidopropyl dimethyl amine XG\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e, Triisopropanolamine XG\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, hexadecyl\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e, tetradecyl XG\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Ester modification also reform XG which have enormous applications such as enhanced water solubility\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e, sustained release\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Carboxy functional group might be the centerpiece for development of amide bond which also used in various applications such as stabilizer and thickness in pharmaceutical formulations\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e, enhance mucoadhesion\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. The hydroxy group of XG could react to aldehyde under acidic conditions to form acetyl linkage lead to enhanced solubility and viscosity\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Sulfoxyamine XG also enhanced viscosity, gelling and mucoadhesion and used in ophthalmic drug delivery system\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Physical and mechanical modification such as dry heating, annealing, moisture and heat treatment also changes physicochemical properties and increase its applications\u003csup\u003e\u003cspan additionalcitationids=\"CR33 CR34\" citationid=\"CR27\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the present investigation, we have modified XG employing chloro acetyl chloride and ammonia. The acetyl amine modified XG was characterized by FTIR, NMR, DSC, XRD and SEM. The modified physical balance method was used for the determination of mucoadhesive characteristics using goat buccal mucosa as a model membrane while other physiochemical properties such as viscosity, gelling and swelling behavior also determined along with acute oral and dermal toxicity.\u003c/p\u003e"},{"header":"2. Material \u0026 Methods","content":"\u003cp\u003eAll ingredients were purchased from regional distributors and from LOBA Chemie Pvt. Ltd, Mumbai, India. Melting points were found to be uncorrected.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthical Clearance\u003c/em\u003e\u003c/strong\u003e:\u0026nbsp;The protocol operated in this study regarding the use of rats as an animal model for acute oral and dermal toxicity was affirmed by the Institutional Animal Ethical Committee, GIPER, Limb, Satara.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.1\u0026nbsp;\u0026nbsp;Synthesis\u003csup\u003e36\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePreparation of Chloroacetyl Xanthan gum:\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChloroacetyl\u0026nbsp;xanthan gum was formulated by treating 10 gm xanthan gum with 100 ml pyridine. 5 ml\u0026nbsp;chloroacetyl\u0026nbsp;chloride was added to above mixture slowly with stirring.\u0026nbsp;Stirring was done for further 2 hours\u0026nbsp;and leave the reaction mixture overnight for digestion. Filtered residue was washed using rectified spirit and dried.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePreparation of acetyl amine xanthan gum\u003c/em\u003e\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e10 gm of chloro-acetyl xanthan gum was dispersed in a flask containing in 50 ml rectified spirit. \u0026nbsp;The 10 ml ammonia solution was added with shaking. After 2 hours stirring mixture was filtered and washed with rectified spirit. The solid residue was dried and used for further activity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Characterization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e2.2.1.1\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cstrong\u003e\u003cem\u003eFourier transform infra- red spectroscopy:\u003c/em\u003e\u003c/strong\u003e BRUKAR FT-IR alpha ATR spectrometer was used for spectral determination of MXG and XG.\u003c/p\u003e\n\u003cp\u003e2.2.1.2\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cstrong\u003e\u003cem\u003eProton Nuclear Magnetic Resonance:\u003c/em\u003e\u003c/strong\u003e VARIAN MERCURI YH-300 NMR Spectroscopy machine used for analysis of \u003csup\u003e1\u003c/sup\u003eH-NMR spectra of MXG and XG. TMS was used as Internal standard. The solvent for xanthan gum and amino acetyl xanthan gum is D\u003csub\u003e2\u003c/sub\u003eO.\u003c/p\u003e\n\u003cp\u003e2.2.1.3\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cstrong\u003e\u003cem\u003eDifferential Scanning Calorimetry (DSC):\u003c/em\u003e\u003c/strong\u003e\u0026nbsp; Thermogram for XG and MXG were reported in 40\u003csup\u003e0\u003c/sup\u003eC \u0026ndash; 300\u003csup\u003e0\u003c/sup\u003eC temperature range at a heating rate 10 \u003csup\u003e0\u003c/sup\u003eC/min.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.2.1.4\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cstrong\u003e\u003cem\u003eX-ray diffraction:\u003c/em\u003e\u003c/strong\u003e X-ray diffractometer (Bruker AXS D8 Advance) along with copper K\u0026alpha;-radiation produced at35 mA and 40 K v in the differential angle range of 3-60 (2\u0026theta;) were used for recording X-ray diffraction of MXG.\u003c/p\u003e\n\u003cp\u003e2.2.1.5\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003cstrong\u003e\u003cem\u003eScanning Electron Microscopy:\u003c/em\u003e\u003c/strong\u003e\u0026nbsp; \u0026nbsp;XG and MXG surface morphology and shape were analyzed using scanning electron microscope. The gold coated samples were mounted on aluminum stub having double layer carbon adhesive tape. The electron micrographs were measured at10 kv accelerated voltage.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Physiochemical Evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.1\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Evaluation of mucoadhesive strength of gel\u003csup\u003e37\u003c/sup\u003e:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eModified physical balance method was used to evaluate comparative mucoadhesive strength of MXG gel. The goat buccal mucosa was collected from the slaughter house and cleaned to remove the underlining fat and loose tissue. The membrane was washed with distilled water and then with simulated saliva having pH 6.8 at 37 \u003csup\u003eo\u003c/sup\u003eC. On the vial with rubber closure was coated by immersing into standard and test mucoadhesive agent solution (1% w/v). One end of the vial was attached with nylon thread and provision was given to raise the weight at other end. Weight was put on at specific time intervals to separate mucous from glass plate. The time and weight required to detach from the buccal mucosa was recorded as the ex vivo bio adhesion time and detachment force respectively. The result was reported as an average of six observations. The force of adhesion was calculated as\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eForce of adhesive= 0.00981/2\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.2\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Viscosity\u003csup\u003e38\u003c/sup\u003e:\u0026nbsp;\u003c/strong\u003eBrookfield viscometer (Brookfield DV-E Vis-cometer) were used for determination of the viscosity of xanthan gum and modified xanthan gum viscosity using spindle L4 at 50 and 100rpm speeds.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.3\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Gelling Property\u003csup\u003e36\u003c/sup\u003e:\u0026nbsp;\u003c/strong\u003eGelling property was determined as previously described method. The solution of Acetyl amine xanthan gum and xanthan gum (0.2\u0026ndash;1%, w/v) in water were prepared in test tube and left for overnight. The consistency of gel in test tubes were examined by tilting at 90\u003csup\u003eo\u003c/sup\u003e and categorized them as solutions, viscous solution or gels on the basis of visual inspection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.4\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Gelling Capacity\u003csup\u003e36\u003c/sup\u003e:\u0026nbsp;\u003c/strong\u003eXG and MXG were examined for gelling capacity by incorporating a solution drop in a vial having newly prepared 2 ml mimicked tear fluid. \u0026nbsp;The time required for its gelling was inspected visually.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.5\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Swelling Index\u003csup\u003e39\u003c/sup\u003e:\u0026nbsp;\u003c/strong\u003eGravimetrically determined water uptake of modified xanthan gum. 30 mg disc (prepared by a hydraulic single punch press, diameter 5.0-mm) was fixed on a small mesh and immersing them into saliva solution (pH 6.75 at 37\u0026plusmn;0.5\u0026ordm;C) in a beaker, weighing of the disc at preplanned time points. Excess water from the swollen discs were evacuated before measuring, Water-uptake \u0026nbsp;was calculated using following formula:\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"data:image/png;base64,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\" width=\"272\" height=\"84\"\u003e\u003c/p\u003e\n\u003cp\u003eWhere, \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Wt=Disc Wt. at given time.\u003c/p\u003e\n\u003cp\u003eWo=Initial Wt.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.6\u0026nbsp; \u0026nbsp;\u0026nbsp;Toxicological Study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.6.1 Acute Oral toxicity\u003csup\u003e40\u003c/sup\u003e:\u0026nbsp;\u003c/strong\u003eIt was performed as per\u003cstrong\u003eOECD-423\u0026nbsp;\u003c/strong\u003eguidelines\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003eIn brief, the\u0026nbsp;healthy young adult female rats ranging between 8- 12 weeks and having 140 \u0026plusmn; 10 gm weight were used. The temperature and the relative humidity of room where maintained at 22\u0026plusmn;3\u003csup\u003e0\u003c/sup\u003eC and 50% respectively. Artificial lighting with 12 hours light, 12 hours dark condition and plenty of drinking water along with laboratory diets were provided. The animals were kept for 10 days under laboratory conditions prior to begin of the study. Rats were selected randomly for the study and marked them for individual identification. Animals were fasted before dosing. The dose was decided on the basis of charts. The test substance was administered in lesser quantity for a period not more than 6 hours. Each step involved three animals. The dose level to be used as the starting dose is selected as 2000 mg/kg body weight as per flow charts of Annex 2. Animals were observed immediately after dosing during the first 30 minutes,\u0026nbsp;and periodically during the first 24 hours. Special attention was given during the first 4 hours, and daily thereafter, for a total of 14 days. All observations were systematically recorded and individual records being maintained for each animal. \u0026nbsp;Additional observations such as changes in skin and fur, eyes and mucous membranes, tremors, convulsions, salivation, diarrhea, lethargy and coma, and also respiratory, circulatory and behavior pattern also being recorded. Individual weights of animals were determined on the day of, or immediately prior to the administration of the test substance and at least weekly thereafter.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3.6.2\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Acute dermal toxicity\u003csup\u003e41\u003c/sup\u003e:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;It was performed as perOECD-434guidelines\u003cstrong\u003e.\u003c/strong\u003eThe healthy young adult female rats ranging between 8- 12 weeks and having 140 \u0026plusmn; 10 gm weight were used.\u0026nbsp;With the help of shaving or clipping fur of test animals were removed from the dorsal regionof the trunk before 24 hours of the study. While removing fur of animals, area was decided on basis of weight of individual animal. The test sample along with porous gauze dressing and non-irritating tape was applied on an area which is about 10 % of the total body surface area for 24 hours. Covering of test site was done in a manner to retain test sample and the gauze dressing, further sample was removed after exposure by using water. On the basis of chart, 2000 mg/kg fixed starting dose was decided. All animals were normally observed for 14 days. Observation of animals were done within first 30 minutes, including particular attention during the first 4 hours, and every day later on for 14 days. All observations were systematically recorded, with individual records being maintained for each animal. \u0026nbsp;Additional observations such as changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern also being recorded. Individual weights of animals were determined on the day of, or immediately prior to the administration of the test substance and at least weekly thereafter.\u003c/p\u003e"},{"header":"3 Results \u0026 Discussion","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Synthesis\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe melting point of acetyl amine xanthan gum was found to be 210 \u003csup\u003e0\u003c/sup\u003eC whereas chloro acetyl Xanthan gum was 165\u0026ndash;170 \u003csup\u003e0\u003c/sup\u003eC and decomposition point of Xanthan gum was 220 \u003csup\u003e0\u003c/sup\u003eC. This difference indicate the formation of product.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Characterization\u003c/h2\u003e \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e \u003ch2\u003e3.2.1 Fourier transform infra- red spectroscopy:\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFT-IR spectral analysis of XG and MXG were recorded on a BRUKAR FT-IR alpha ATR spectrometer. Xanthan gum exhibit a wide band of absorption at 3332 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e because of OH group bonded to various degree. Peak at 2918 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003efor CH aliphatic stretching was observed. The presence of absorption band at 1716 \u0026amp; 1602 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e can be attributed to carboxyl group stretching of alkyl ester \u0026amp; asymmetric stretching of carboxylate ion. C-O-C of cyclic ether and\u0026ndash;CH of methyl exhibit absorption band at 1020 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e and 1406 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e respectively due to bending vibrations. MXG exhibit absorption band at 3250 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e due to NH\u003csub\u003e2\u003c/sub\u003e group. The broad shape of xanthan gum due to OH group changes into sharp spikes indicating occurrence of substitution on xanthan gums hydroxyl group. The peak at 2893 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e and 1400 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e observed due to CH stretching and alkanes bending. The peak at 1018 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e was observed due to stretching of cyclic ether. Decreased hydroxyl groups signal intensity contributed the fact that the concentration of hydroxyl functions dropping in the XG.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003e3.2.2 Proton Nuclear Magnetic Resonance:\u003c/h2\u003e \u003cp\u003eIn the NMR spectra, peak at δ 2.038 indicate CH\u003csub\u003e3\u003c/sub\u003e protons of acetate part of XG. The broad peak at δ 3.55 \u0026amp; δ 3.90 are due to hydroxyl groups present on glucose \u0026amp; mannose units. The protons of glucose \u0026amp; mannose residues are observed at δ 4.78 ppm. In case of modified xanthan gum, the methyl protons of acetate part are found at δ 1.95. The protons of glucose \u0026amp; mannose residues are observed at δ 4.5. The hydroxyl groups are disappeared in a modified xanthan gum indicate substitution of acetyl amine take place on xanthan gum. The broad peak at δ 8.00 are due to the amino group whereas peaks at δ 8.5 \u0026amp; δ 8.9 are due to the methylene groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e3.2.3 Differential Scanning Calorimetry (DSC):\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAs per DSC spectrum, the thermogram of XG shows a broad endotherm at 82.47 \u003csup\u003e0\u003c/sup\u003eC whereas MXG shows endothermic peak at 88.35 \u003csup\u003e0\u003c/sup\u003eC. XG shows DSC curve similar to amorphous material which is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. In case of MXG, extra endothermic peak at 220 \u003csup\u003e0\u003c/sup\u003eC was observed which may be due to the modification.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e3.2.4 X-ray diffraction:\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe findings of DSC study were in accordance with X-ray study results. The MXG had a typical crystalline type diffractogram with the distinctive peak appearing at 19, 30, 41 and 51 \u003cb\u003e2θ\u003c/b\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e3.2.5 Scanning Electron Microscopy:\u003c/h2\u003e \u003cp\u003eThe SEM photographs of XG showed smooth surface with polyhedral arrangement while MXG exhibit spongy surface with roughness. MXG exhibiting SEM image revealed that the substitution of poly acetyl amine on xanthan gum result into alteration of shape and size of parent xanthan gum.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Physiochemical Evaluation\u003c/h2\u003e \u003cp\u003e \u003cb\u003e3.3.1 Mucoadhesion property\u003c/b\u003e: Modified polymer exhibited 0.0703 N adhesion force to separate 1% w/v coated plate from the mucus in 33.91 sec while xanthan gum (Plain polymer) showed 0.0133N adhesion force to separate the plate, in respond to test material towards the mucus in 16.83 second. The water weight for the detachment of modified polymer was found to be 14.33 whereas for xanthan it was 2.74. This result indicate that acetyl amine modified xanthan gum exhibits the longest detachment time, highest water weight for detachment, and requires the greatest force as compared to plain xanthan gum.\u003c/p\u003e \u003cp\u003eMucin or Mucous glycoprotein is the principal components of mucus and having negative charged on its surface residues. Hence ionic interactions are taken place in between negatively charged mucus with cationic primary amine group of xanthan gum leading to superior mucoadhesion property as compared to plain xanthan gum.\u003c/p\u003e \u003cp\u003e \u003cb\u003e3.3.2 Viscosity\u003c/b\u003e: The viscosity of Xanthan gum was modified due to the acetyl amine grafting on Xanthan gum. XG and MXG aqueous solution exhibit pseudoplastic flow behavior. Still MXG showed increased viscosity. It was observed that the viscosity of XG \u0026amp; MXG was increased with higher polymeric concentration, lower speed \u0026amp; temperature. However enhanced viscosity of MXG might be due to contribution of cationic amine character (Acetyl amine group) to its backbone chain, resulting in minimization of coulombic repulsion and increased involvement of backbone chain resulting in improved viscosity.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec18\" class=\"Section3\"\u003e \u003ch2\u003e3.3.2 Gelling Property \u0026amp; Gelling Capacity study\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparative Gelling Property \u0026amp; Gelling Capacity study of Xanthan gum \u0026amp; Modified xanthan gum\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSr. No.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eXG\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMXG\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eGelling property (% w/v)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSolution\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eViscous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGel\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eGelling capacity of solution\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLess than 1 hr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLess than 8 hr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMore than 8 hr\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMore than 12 hrs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMXG exhibits two fold enhancement of gelling property in contrast to the parent XG. The 1% gel prepared by xanthan gum was spread within 1 hour in the solution; while MXG remains as it is for more than 12 hours.\u003c/p\u003e\u003cp\u003e \u003cb\u003e3.3.3 Swelling Index\u003c/b\u003e: Swelling degree is a characteristic of any polymer that control drug loading as well as drug release. Swelling study were performed by monitoring the changes in weight of disc as function of time. MXG showed 0.6gm swelling weight of disc within 10 min whereas XG showed 0.3gm weight. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e8\u003c/span\u003e, water was absorbed by MXG at a very fast and constant rate during swelling process owing to the high hydrophilicity and capillary action of MXG surface. As per SEM image, MXG having rough and spongy surface. These interconnected pores played important role in promoting a high swelling rate and effective water retention.\u003c/p\u003e\u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section3\"\u003e \u003ch2\u003e3.3.4 Toxicological study:\u003c/h2\u003e \u003cp\u003e \u003cstrong\u003eAcute Oral Toxicity\u003c/strong\u003e \u003cp\u003eXanthan gum is generally recognized as a safe for food application because it induced low or minimal toxic effect. OECD guideline 423 was used to study acute oral toxicity of modified xanthan gum. 2000 mg/kg weight from flow chart of Annex. 2c was considered while selecting dose. At this dose level, from group, no mortality was observed in three animals of a group at this dose. No mortality specify LD\u003csub\u003e50\u003c/sub\u003e value of modified xanthan gum was more than 2000 mg/kg which indicates that MXG having less acute toxicity similar to xanthan gum.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eAcute dermal Toxicity\u003c/strong\u003e \u003cp\u003eOECD guideline 434 was also used to determine acute dermal toxicity of MXG. No mortality were observed at 2000mg/ kg dose level when gel was applied on skin of rat. There are no any changes in skin \u0026amp; fur, eyes observed. Other parameters such as any tremors, convulsion, salivation, diarrhea, sleep \u0026amp; coma were not observed in the animal.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"4 Conclusion","content":"\u003cp\u003eThe derivatization of acetyl amine group on xanthan gum was achieved successfully by treating xanthan gum with chloro acetyl chloride in basic environment and then reacted with ammonia. The characterization of modification was confirmed by FTIR, H-NMR, DSC, XRD \u0026amp; SEM spectra. These spectral evidences indicate that the modification on XG was successfully achieved. Acetyl amine grafted XG showed superior physiochemical properties as compared to the plain XG. The enhancement of viscosity and mucoadhesion of MXG was observed due to cationic acetyl amino group present on backbone of XG. The result of ex vivo bio adhesion studies reveal a significant increase in mucosal detachment time as compared to plain polymer indicate the more mucoadhesion application of acetyl amine grafted polymer. MXG from gel at concentration of 0.6% whereas for XG it requires 1.2% concentration. The 1% gel of MXG remain in solution for more than 12 hours indicate that gelling capacity was also increased. The water absorption by MXG at a very fast rate due to the higher hydrophilicity and capillary action. The force of detachment of MXG was more as compared to XG indicate the more mucoadhesion property. The LD50 value of MXG was more than 2 gm/kg indicate less oral toxicity No any changes were observed after application on skin indicate safe for dermal application. Therefore this grafted polymer might be well exploited as a potential carrier for various oral as well as dermal drug delivery system in future.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflicts of interest:\u003c/h2\u003e \u003cp\u003eThe authors confirm that there are no known conflicts of interest associated with this publication.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eThis work was carried out in collaboration among all authors. Author Neelam Singla designed the study. Author Manisha Patil performed the laboratory research work, wrote manuscript. All authors read and approved the final manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJ Patel, B Maji, NS Hari Narayana Moorthy, and S Maiti, \u003cstrong\u003e\u003cem\u003eRSC Adv.\u003c/em\u003e\u003c/strong\u003e, \u003cstrong\u003e10, \u003c/strong\u003e27103-27136 (2020). https://doi.org/10.1039/D0RA04366D.\u003c/li\u003e\n\u003cli\u003eS Gao, Z Zhang, S Li, H Su, L Tang, Y Tan, W Yu, F Han, \u003cem\u003eInt. J. Biol. Macromol.\u003c/em\u003e 120:729\u0026ndash;735 (2018). https://doi.org/10.1016/j.ijbiomac.2018.08.164\u003c/li\u003e\n\u003cli\u003eMM Yahoum, S Toumi, H Tahraoui, S Lefnaoui, A Hadjsadok, A Amrane, M Kebir, J Zhang, AA Assadi and L Mouni, \u003cem\u003eSustainability\u003c/em\u003e, 15: 6345 (2023). https://doi.org/10.3390/su15086345. \u003c/li\u003e\n\u003cli\u003eJ Wang, S Nie, \u003cem\u003eTrends Food Sci. Technol.\u003c/em\u003e 87:35\u0026ndash;46 (2019). https://doi.org/10.1016/j.tifs.2018.02.005.\u003c/li\u003e\n\u003cli\u003eF Garc\u0026iacute;a-Ochoa , VE Santos , JA Casas and E G\u0026oacute;mez , \u003cem\u003eBiotechnol. Adv.\u003c/em\u003e, 18:549 \u0026mdash;579 (2000). https://doi.org/10.1016/S0734-9750(00)00050-1 \u003c/li\u003e\n\u003cli\u003eAF D\u0026aacute;rio , LMA Hort\u0026ecirc;ncio , MR Sierakowski , JC Queiroz Neto and DFS Petri , \u003cem\u003eCarbohydr. Polym.\u003c/em\u003e, 84:669 \u0026mdash;676 (2011). https://doi.org/10.1016/j.carbpol.2010.12.047 .\u003c/li\u003e\n\u003cli\u003eT Riaz, MW Iqbal, B Jiang, J Chen, \u003cem\u003eInt. J. Bio\u003c/em\u003e\u003cem\u003e,\u003c/em\u003e\u003cem\u003e. Macromol\u003c/em\u003e, 186:472\u0026ndash;489 (2021). https://doi.org/10.1016/j.ijbiomac.2021.06.196\u003c/li\u003e\n\u003cli\u003eTA Camesano and KJ Wilkinson, \u003cem\u003eBiomacromolecules\u003c/em\u003e, \u003cstrong\u003e2:\u003c/strong\u003e1184-1191 (2001) . https://doi.org/10.1021/bm015555g\u003c/li\u003e\n\u003cli\u003eH Li , W Hou and X Li , \u003cem\u003eCarbohydr. Polym.\u003c/em\u003e, \u003cstrong\u003e89\u003c/strong\u003e :24-30 (2012). https://doi.org/10.1016/j.carbpol.2012.02.022 \u003c/li\u003e\n\u003cli\u003eVB Junyaprasert and G Manwiwattanakul, \u003cem\u003eInt. J. Pharm.,\u003c/em\u003e 81-91 (2008). https://doi.org/10.1016/j.ijpharm.2007.10.018\u003c/li\u003e\n\u003cli\u003eB Katzbauer, \u003cem\u003ePolym. Degrad. Stab.,\u003c/em\u003e 81-84 (1998). https://doi.org/10.1016/S0141-3910(97)00180-8. \u003c/li\u003e\n\u003cli\u003eA Palaniraj and V Jayaraman, \u003cem\u003eJ. Food Eng.,\u003c/em\u003e 106:1\u0026ndash;12 (2011), https://doi.org/10.1016/j.jfoodeng.2011.03.035.\u003c/li\u003e\n\u003cli\u003eYL Yang, L Ding, J Zhang, YL Zhang, J Yao and DF Cui, \u003cem\u003eJ. Northwest Norm. Univ.,\u003c/em\u003e 37: 70\u0026ndash;72 (2001).\u003c/li\u003e\n\u003cli\u003eV Rana, P Rai, \u003cem\u003eCarbohydr. Polym., \u003c/em\u003e83:1031 (2011). DOI:\u003cu\u003e10.1016/j.carbpol.2010.09.010\u003c/u\u003e.\u003c/li\u003e\n\u003cli\u003eM Ahuja, A Kumar, K Singh, \u003cem\u003eInt. J. Biol. Macromol., 51:\u003c/em\u003e1086-1090 (\u003cstrong\u003e2012)\u003c/strong\u003e. https://doi.org/10.1016/j.ijbiomac.2012.08.023 \u003c/li\u003e\n\u003cli\u003eQ Zhang, XM Hu, MY Wu, MM Wang, YY Zhao, TT Li, \u003cem\u003eReactive and Functional Polymers\u003c/em\u003e, 136:34\u0026ndash;4 (2019). https://api.semanticscholar.org/CorpusID:104369698 \u003c/li\u003e\n\u003cli\u003eL Shuang, Z Hong, F Bo, L Yongjun, Q Xiaohui and Z Wen, \u003cem\u003eDrilling and Completion Fluids,\u003c/em\u003e 34:107\u0026ndash;116 (2017), DOI: 10.3969/j.issn.1001- 5620.2017.05.020.\u003c/li\u003e\n\u003cli\u003eL Chengcheng, F Bo, L Yongjun, Q Xiaohui, Z Wen and W Liwei, \u003cem\u003eOil\u003c/em\u003e\u003cem\u003e Fi\u003c/em\u003e\u003cem\u003eeld Chemistry,\u003c/em\u003e 35:628\u0026ndash;633 (2018). https://doi.org/10.1021/acs.energyfuels.1c02941\u003c/li\u003e\n\u003cli\u003eS Maiti, S Mukherjee and R Datta, \u003cem\u003eInt. J. Biol. Macromol.,\u003c/em\u003e 70:20\u0026ndash;25 (2014). https://doi.org/10.1016/j.ijbiomac.2014.06.031\u003c/li\u003e\n\u003cli\u003eH Quan, Y Hu, Z Huang and D Wenmeng, \u003cem\u003eJ. Dispersion Sci. Technol\u003c/em\u003e., 41:656\u0026ndash;666 (2020). https://doi.org/10.1080/01932691.2019.1610425\u003c/li\u003e\n\u003cli\u003eXL Qian, WH Wu, PZ Yu and JQ Wang, \u003cem\u003eJ. Beijing Inst. Technol.,\u003c/em\u003e 16:346\u0026ndash;351 (2007).\u003c/li\u003e\n\u003cli\u003eXL Qian, JZ Su, WH Wu and CM Niu, \u003cem\u003eOil\u003c/em\u003e\u003cem\u003efi\u003c/em\u003e\u003cem\u003eeld Chemistry,\u003c/em\u003e 24:154\u0026ndash; 157 (2007).\u003c/li\u003e\n\u003cli\u003eY Tao, R Zhang, W Xu, Z Bai, Y Zhou, S Zhao, Y Xu and DQ Yu, \u003cem\u003eFood Hydrocolloids,\u003c/em\u003e 52:923\u0026ndash;933 (2016), https://doi.org/10.1016/j.foodhyd.2015.09.006\u003c/li\u003e\n\u003cli\u003eM Bhatia, M Ahuja and H Mehta, C\u003cem\u003earbohydr. Polym.,\u003c/em\u003e 131:119-124 (2015), https://doi.org/10.1016/j.carbpol.2015.05.049\u003c/li\u003e\n\u003cli\u003eB Wang, Y Han, Q Lin, H Liub, C Shen, K Nan and H Chen, \u003cem\u003eJ. Mater. Chem. B\u003c/em\u003e, 4:1853\u0026ndash;1861 (2016), http://dx.doi.org/10.1039/C5TB02046H\u003c/li\u003e\n\u003cli\u003eA Roy, S Comesse, M Grisel, N Hucher, Z Souguir and F Renou, \u003cem\u003eBiomacromolecules\u003c/em\u003e, 15:1160\u0026ndash;1170 (2014), https://doi.org/10.1021/bm4017034\u003c/li\u003e\n\u003cli\u003eF Laffleur and M Michalek, \u003cem\u003eInt. J. Biol. Macromol,\u003c/em\u003e 102:1250\u0026ndash;1256 (2017), https://doi.org/10.1016/j.ijbiomac.2017.04.123.\u003c/li\u003e\n\u003cli\u003eC Menzel, M Jelkmann, F Laffleur and A Bernkop- Schn\u0026uml;urch, \u003cem\u003eInt. J. Pharm.,\u003c/em\u003e 517:196\u0026ndash;202 (2017), https://doi.org/10.1016/j.ijpharm.2016.11.055.\u003c/li\u003e\n\u003cli\u003eL Su, WK Ji, WZ Lan and XQ Dong, \u003cem\u003eCarbohydr. Polym.,\u003c/em\u003e 53:497\u0026ndash;499 (2003), https://doi.org/10.1016/S0144-8617(02)00287-4\u003c/li\u003e\n\u003cli\u003eRL Jadhav, MV Patil and SN Shaikh, \u003cem\u003eInternational Journal of Lifescience and Pharma Research,\u003c/em\u003e 10:3: 20-28 (2020). https://doi.org/10.22376/ijpbs/lpr.2020.10.3.P20-28 \u003c/li\u003e\n\u003cli\u003eRL Jadhav, P Beloshe, AV Yadav, MV Patil and SN Shaikh, \u003cem\u003eAsian Journal of Pharmaceutics\u003c/em\u003e, 14(2): 236 \u0026ndash; 246 (2020). DOI: http://dx.doi.org/10.22377/ajp.v14i2.3619\u003cem\u003e.\u003c/em\u003e\u003c/li\u003e\n\u003cli\u003eMA Zirnsak, DV Boger and V Tirtaatmadja, \u003cem\u003eJ. Rheol.,\u003c/em\u003e 43:627\u0026ndash;650 (1999), https://doi.org/10.1122/1.551007.\u003c/li\u003e\n\u003cli\u003eNM Sereno, SE Hill and JR Mitchell, \u003cem\u003eCarbohydr. Res\u003c/em\u003e., 342:1333\u0026ndash;1342 (2007), https://doi.org/10.1016/j.carres.2007.03.023.\u003c/li\u003e\n\u003cli\u003eTJ Foster and JR Mitchell, Physical Modification of xanthan gum, in Gums and Stabilisers for Food Industry, ed. P. A. Williams and G. O. Phillips, RSC Publishing, 77-88 (2012). DOI: 10.1039/9781849734554.\u003c/li\u003e\n\u003cli\u003eJS Disha, MHA Begum, MMAK Shawan, N Khatun, S Ahmed, MS Islam, MR Karim, M. R. L. Islam, M. M. Hossain and M. A. Hasan, \u003cem\u003eRes. J. Mater. Sci\u003c/em\u003e., 4:13\u0026ndash;18 (2016).\u003c/li\u003e\n\u003cli\u003eRL Jadhav, AV Yadav, MV Patil,\u003cem\u003e Asian Journal of Chemistry. \u003c/em\u003e31(12):127-132 (2019). https://doi.org/10.14233/ajchem.2020.22300\u003c/li\u003e\n\u003cli\u003eH Mahajan, H Shaikh, S Gattani, \u0026amp; P Nerkar, \u003cem\u003eInt J pharm Sci nanotech\u003c/em\u003e, 2(2): 544-50 (2009). https://doi.org/10.37285/ijpsn.2009.2.2.8\u003c/li\u003e\n\u003cli\u003eLaffleur Flavia and Michalek Martina, \u003cem\u003eInt J Biol Macromol\u003c/em\u003e , 6;102:1250-1256 (2017). https://doi.org/10.1016/j.ijbiomac.2017.04.123\u003c/li\u003e\n\u003cli\u003eS Sudarshan, BB Sunil. \u003cem\u003eBrazilian Journal of Pharmaceutical Sciences\u003c/em\u003e. 51:689-98 (2015). https://doi.org/10.1590/S1984-82502015000300021\u003c/li\u003e\n\u003cli\u003eOECD (2002), \u003cem\u003eTest No. 423: Acute Oral toxicity - Acute Toxic Class Method\u003c/em\u003e, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, https://doi.org/10.1787/9789264071001-en .\u003c/li\u003e\n\u003cli\u003eOECD Guideline for testing of chemicals, Proposal for a new Draft Guideline 434: Acute Dermal toxicity. 2004; 1-13\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Polyacetyl amine grafted xanthan gum, Polymer modification, Modified xanthan gum, Mucoadhesive polymer, gelling agent, viscosity modifier","lastPublishedDoi":"10.21203/rs.3.rs-4168726/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4168726/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePolyacetal amine grafted xanthan gum was synthesized by treating xanthan gum with chloroacetyl chloride which resulted in an intermediate to which ammonia was reacted. Proton NMR and IR spectrum confirmed the formation of poly-acetyl amine grafting on xanthan gum (MXG). The crystallinity of MXG was confirmed by DSC and XRD. SEM image indicates that the smooth polyhedral structure of xanthan gum changed to a rough spongy surface in MXG along with size and shape. Comparative mucoadhesion evaluation of MXG using goat buccal mucosa revealed higher ex vivo bio adhesion time as compared to xanthan gum. This improved mucoadhesion property of MXG can be attributed to the formation of attractive force between negative charge mucus and positive charged amine functionality. However, grafted polyhedral amine into xanthan gum backbone also enhanced other physiochemical properties such as viscosity, gelling property and swelling index etc. Acute oral toxicity and dermal toxicity studies reveals the safety of MXG. Therefore, this grafted polymer might be well exploited as a potential polymer for various drug delivery systems.\u003c/p\u003e","manuscriptTitle":"Poly acetyl amine grafted xanthan gum: Synthesis, Characterization and evaluation as Mucoadhesive Polymer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-04 17:31:35","doi":"10.21203/rs.3.rs-4168726/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"811cdf5e-187b-48db-9375-7a23e7a07379","owner":[],"postedDate":"April 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-09T02:02:41+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-04 17:31:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4168726","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4168726","identity":"rs-4168726","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}