Non-nuke HIV-1 inhibitor shuttled by mesoporous silica nanoparticles effectively slows down HIV-1 replication in infected human cells

The objectives of this study were to reduce the cytotoxic effect of nevirapine (NVP) and to enhance its anti-HIV efficacy through mesoporous silica nanoparticles (MSNPs) mediated delivery. MSNPs were synthesized and characterized by various techniques. Confocal microscopy and flow cytometry results exhibited efficient uptake of FITC-conjugated MSNPs in TZM-bl cells. The NVP was loaded within MSNPs, and its anti-HIV1 efficacy was assessed on HIV1 (R5 and X4 variants) infected TZM-bl cells and further confirmed on peripheral blood mononuclear cells (PBMCs). The in vitro assessment of the anti-HIV1 potential of NVP and NVP-MSNPs in HIV1 infected TZM-bl cells and PBMCs showed increased efficacy of NVP upon loading within MSNPs with significant increase in therapeutic index. The increased efficacy against HIV1 was accompanied by reduced cytotoxicity to TZM-bl cells and PBMCs. Further, reverse transcriptase (RT) assay confirmed the inhibitory effect on RTase, which is a key enzyme in HIV-1 replication. The present study showed that entrapment of NVP within MSNPs led to an increased efficacy with reduced cytotoxic effect resulting in the enhanced therapeutic index (TI).