Lipid nanocarrier targeting activated macrophages for antiretroviral therapy of HIV reservoir.

Abstract

Aim: To develop lipid nano-antiretrovirals (LNAs) for the treatment of HIV-infected macrophages. Materials & methods: LNAswere prepared with docosahexaenoic acid to facilitate brain penetration and surface-decorated with folate considering that infected macrophages often overexpress folate receptors. Results: Folate-decorated LNAs loading rilpivirine (RPV) wereefficiently taken up byfolate receptor-expressing cell types including activated macrophages. The intracellular Cmax of theRPV-LNAs in activated macrophages was 2.54-fold and the area under thecurve was3.4-fold versus free RPV, translating to comparable or higher (p<0.01; RPV ≤6.5ng/ml) activities against HIV infectivity and superior protection (p<0.05) against HIV cytotoxicity. LNAs were also effective in monocyte-derived macrophages. Conclusion: These findings demonstratethe potential of LNAs for the treatment of infected macrophages, which are key players in HIV reservoirs.