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

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.

• Authors: Lin Mei, Junbo Bao, Lina Tang, Chao Zhang, Hai Wang, Leilei Sun, Guilei Ma, Laiqiang Huang, Jing Yang, Linhua Zhang, Kexin Liu, Cunxian Song, Hongfan Sun
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 39 Issue 5 Pg. 421-7 (Mar 18 2010) ISSN: 1879-0720 [Electronic] Netherlands
• PMID: 20132884 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

• Drug Implants
• Hormone Antagonists
• Mifepristone

Topics

• Animals
• Disease Models, Animal
• Drug Implants
• Endometriosis (drug therapy)
• Female
• Hormone Antagonists (administration & dosage, pharmacokinetics, therapeutic use)
• In Vitro Techniques
• Microscopy, Electron, Scanning
• Mifepristone (administration & dosage, pharmacokinetics, therapeutic use)
• Molecular Weight
• Rats
• Rats, Wistar
• Spectroscopy, Fourier Transform Infrared