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.