A biodegradable long-term contraceptive implant with steady levonorgestrel release based on PLGA microspheres embedded in PCL-coated implant

Abstract

The biodegradable subcutaneous implants of levonorgestrel (LNG) have emerged as the most promising agents in long-term contraception, but there are still problems with burst release of drugs and unsteady LNG concentrations in blood. In this study, the aim was the development of biodegradable LNG implants for steady LNG release. Specifically, LNG was firstly loaded in biodegradable poly (lactic-co-glycolic acid) (PLGA) microspheres by emulsion-solvent evaporation method. The size, encapsulation efficiency (EE) and drug loading (DL) of microspheres were ∼3 μm, 83.71 ± 3.59% and 11.12 ± 0.47%, respectively. Then, the LNG-PLGA microspheres were directly compressed into tablets and subsequently coated with polycaprolactone (PCL) to prolong drug release duration, achieving LNG-PLGA-PCL tablets used as contraceptive implants. In vitro release studies demonstrated LNG-PLGA-PCL implant can continuously and steady release LNG for 90 days. After subcutaneous implantation, such tablets showed more steady drug plasma concentration and longer retention in vivo than those of subcutaneous injection microspheres. Moreover, these in vivo properties of LNG-PLGA-PCL implant are comparable to the commercial subcutaneous implanted LNG-silicone rods. Summarily the LNG-PLGA-PCL implant displayed long-term controlled release and outstanding biodegradation properties, which could be promising for avoiding secondary injury to users and reasonably considered as a candidate to replace commercial LNG-silicone rods in future.