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

To develop lipid nano-antiretrovirals (LNAs) for the treatment of HIV-infected macrophages. LNAs were prepared with docosahexaenoic acid to facilitate brain penetration and surface-decorated with folate considering that infected macrophages often overexpress folate receptors. Folate-decorated LNAs loading rilpivirine (RPV) were efficiently taken up by folate receptor-expressing cell types including activated macrophages. The intracellular C of the RPV-LNAs in activated macrophages was 2.54-fold and the area under the curve was 3.4-fold versus free RPV, translating to comparable or higher (p < 0.01; RPV ≤6.5 ng/ml) activities against HIV infectivity and superior protection (p < 0.05) against HIV cytotoxicity. LNAs were also effective in monocyte-derived macrophages. These findings demonstrate the potential of LNAs for the treatment of infected macrophages, which are key players in HIV reservoirs.