efavirenz loaded nanostructured lipid carriers for efficient and prolonged viral inhibition in hiv-infected macrophages

Background: the clinical outcome of anti-hiv therapy is poor due to the inherent fallouts of anti-hiv therapy. it is further worsened due to the presence of viral reservoirs in immune cells like the macrophages. an ideal anti-hiv therapy must reach, deliver the drug and exert its action inside macrophages. to address this, we developed novel cationic nanostructured lipid carriers of efavirenz (cationic efv-nlc). methods: the developed cationic efv nlcs were evaluated for particle size, zeta potential, encapsulation efficiency, in-vitro drug release, dsc, xrd, tem, cytotoxicity, cellular uptake studies and anti-hiv efficacy in a monocyte-derived macrophage cell line (thp-1). results: cationic efv-nlcs showed high encapsulation efficiency (90.54 ± 1.7%), uniform particle size distribution (pdi 0.3-0.5 range) and high colloidal stability with positive zeta potential (+23.86 ± 0.49 mv). dsc and xrd studies confirmed the encapsulation of efv within nlcs. cytotoxicity studies (mtt assay) revealed excellent cytocompatibility (cc50 13.23 ± 0.54 μg/ml). fluorescence microscopy confirmed the efficient uptake of cationic efvnlcs, while flow cytometry revealed time and concentration dependant uptake within thp-1 cells. cationic efv-nlcs showed higher retention and sustained release with 2.32-fold higher percent inhibition of hiv-1 in infected macrophages as compared to efv solution at equimolar concentrations. interestingly, they demonstrated 1.23-fold superior anti-hiv efficacy over efvloaded nlcs at equimolar concentrations. conclusion: cationic nlcs were capable of inhibiting the viral replication at higher limits consistently for 6 days suggesting successful prevention of hiv-1 replication in infected macrophages and thus can prove to be an attractive tool for promising anti-hiv therapy.