Preparation and evaluation of amphipathic lipopeptide‐loaded PLGA microspheres as sustained‐release system for AIDS prevention

At present, AIDS drugs are typical inhibitors that cannot achieve permanent effects. Therefore, the research of blocking HIV infection is essential. Especially for people in the high‐risk environment, long‐term prevention is important, because HIV can easily infect cells once the drug is interrupted. However, there is still no long‐acting AIDS prevention drug approved. Hence, the purpose of this study is to prepare a fusion inhibitor loaded poly(d, l‐lactic‐co‐glycolic acid) (PLGA) microspheres as a sustained‐release system for long‐term AIDS prevention. As the HIV membrane fusion inhibitor (LP‐98) used in this research is amphiphilic lipopeptide, W(1)/O/W(2) double‐emulsion method was chosen, and premix membrane emulsification technique was used for controlling the uniformity of particle size. Several process parameters that can impact drug loading efficiency were summarized: the concentration of LP‐98 and PLGA, and the preparation condition of primary emulsion. Finally, the microspheres with high loading efficiency (>8%) and encapsulation efficiency (>90%) were successfully prepared under optimum conditions. Pharmacokinetic studies showed that LP‐98‐loaded microspheres were capable to continuously release for 24 days in rats. This research can promote the application of sustained‐release microspheres in AIDS prevention, and the embedding technique used in this study can also provide references for the loading of other amphipathic drugs.