Strategies for transportation of peptides across the skin for treatment of multiple diseases.

ABSTRACT An established view in genetic engineering dictates an increase in the discovery of therapeutic peptides to enable the treatment of multiple diseases. The use of hypodermic needle for delivery of proteins and peptides occurs due to the hydrophilic nature, sensitivity toward proteolytic enzymes and high molecular weight. The non-invasive nature of the transdermal delivery technique offers multiple advantages over the invasive route to release drugs directly into the systemic circulation to enhance bioavailability, better patient compliance, reduced toxicity and local irritability. The transdermal route seems highly desirable from the pharmaco-therapeutic and patient compliance point of view, however, the lipophilic barrier of skin restricts the application. The use of several techniques like electrical methods (iontophoresis, sonophoresis etc.), chemical penetration enhancers (e.g. protease inhibitors, penetration enhancers, etc.) and nanocarriers (dendrimers, lipid nanocapsules, etc.) are utilized to improve the passage of drug molecules across the biomembranes. Additionally, such clinical interventions facilitate the physicochemical characteristics of peptides, to enable effective preservation, conveyance and release of therapeutic agents. Moreover, strategies ensure the attainment of the intended targets and enhance treatment outcomes for multiple diseases. This review article focuses on the techniques of peptide transportation across the skin to advance the delivery approaches and therapeutic efficiency. Peptides show multiple therapeutic advantages for the management of various diseases. However, poor oral bioavailability, interference of digestive enzymes, and patient non-compliance for parenteral administration limits its use. Transdermal delivery shows advantages like higher efficacy, absence of first-pass metabolism compared to oral route, and direct absorption into the bloodstream. Despite the promising potential, the lipophilic barrier of skin, physicochemical properties of peptides restrict the transdermal application. Various strategies are developed for skin penetration of peptides. Utilization of nanocarriers offers enhancement in chemical drug stability and reduction in adverse effects by modulating drug the release. Overall therapeutically effective formulations and optimized carrier systems, will enable successful transdermal delivery systems systems for theranostic applications, and personalized medicine in near future. Peptides demonstrate multiple therapeutic advantages for the management of multiple diseases. However, limited therapeutic efficiency results due to poor oral bioavailability, interference of digestive enzymes, and patient non-compliance for parenteral administration. Various challenges are associated with transdermal delivery of peptides such as skin, physicochemical properties of peptides, etc. The use of external stimulants, permeation aids, chemical modulators, prodrugs aid to overcome the limitations for transdermal delivery of peptides. However, these approaches may not be suitable for cosmetics or sensitive eye areas. Therefore, a gap is identified to develop systems that optimize the delivery of actives into the skin and minimize adverse effects. Nanocarriers offer various advantages like enhancement in chemical drug stability and reduction in adverse effects by modulating the drug release for longer periods. Nanotechnology-based formulations facilitate enhanced topical drug delivery, and maintain the integrity of skin barrier, thus offering superior advantages compared to other approaches. Multiple nanocarrier systems are utilized such as polymeric nanoparticles, liposomes, niosomes, solid lipid nanoparticles, dendrimers, nanostructured lipid carriers, metal-based peptide complexes, microneedles for successful transdermal delivery of peptides. Author contributions J Bhavsar: visualization, writing (original draft). K Kasture: visualization, writing (original draft). BV Salvi: visualization, writing (original draft). P Shende: conceptualization, writing (review and editing), supervision. Financial disclosure This paper was not funded. Competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.