A novel mifepristone-loaded implant for long-term treatment of endometriosis: in vitro and in vivo studies

Lin Mei, Junbo Bao, Bao J, Lina Tang, Tang L, Chao Zhang, Zhang C, Wang H, Hai Wang, Leilei Sun, Sun L, Guilei Ma, Ma G, Huang L, Laiqiang Huang, Jing Yang, Yang J, Zhang L, Linhua Zhang, Liu K, Kexin Liu, Song C, Cunxian Song, Sun H, Hongfan Sun
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2010 · vol. 39(5) , pp. 421–427 · doi:10.1016/j.ejps.2010.01.012 · PMID:20132884 · W2093316184
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Researchers developed and tested a novel mifepristone-loaded implant in vitro and in vivo for potential long-term treatment of endometriosis.

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Abstract

The objective of this study was to prepare a novel mifepristone-loaded PCL/Pluronic F68 implant to achieve long-term treatment of endometriosis. PCL/Pluronic F68 compound (90/10, w/w) with viscosity average molecular weight of 65,000 was successfully synthesized. The end-capped Pluronic F68 was incorporated in PCL matrixes as molecular dispersion without forming a copolymer. The mifepristone-loaded implant made of PCL/Pluronic F68 compound was a cylindrical capsule with an outer diameter of 2.5mm and an inner diameter of 2.2mm. The surface of PCL/Pluronic F68 compound appears porous because Pluronic F68 which is water soluble could leach out due to the water phase. Drug loading of 0.75-, 1.5- and 3.0-cm length implants was 3.05+/-0.18, 6.06+/-0.41 and 11.87+/-0.39mg, respectively. A sustained mifepristone release rate without obvious initial burst and later decline over a period of 180d was observed. The cumulative drug release showed a linear relationship with time, indicating that mifepristone release from the implants followed zero-order kinetics (R(2)>0.99). The data showed that the C(max) and AUC(0-inf) were proportional to imlant length and dose, and all groups reached plasma C(max) at about the same time (approximately 7d) and had similar T(1/2) (approximately 150d) and MRT (approximately 220d). There were obvious inhibitory effects on the growth of endometrial explants in Wister rats in a dose-dependent manner after administration of mifepristone-loaded implants with implant length from 1.5 to 9.0cm for 1-3 months. However, mifepristone-loaded implants with implant length of 12.0cm had no better inhibitory effects on the growth of endometrium when compared with the implants with implant length of 9.0cm (P>0.05). In conclusion, subcutaneous implantation of mifepristone-loaded PCL/Pluronic F68 capsules was proven an effective means for long-term treatment of chronic endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Hormone Antagonists Mifepristone Animals Animals Disease Models, Animal Disease Models, Animal Drug Implants Drug Implants Endometriosis Endometriosis Female Female Hormone Antagonists Hormone Antagonists Hormone Antagonists Hormone Antagonists In Vitro Techniques In Vitro Techniques Microscopy, Electron, Scanning

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (36)

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