Nanostructured lipidic carriers of lopinavir for effective management of HIV-associated neurocognitive disorder

Abstract

The current research work entails the formulation, optimization and evaluation of nanolipidic carriers of an antiretroviral drug, lopinavir for brain targeting to reduce HIV associated neurocognitive disorder. Quality by Design framework was applied for the development of nanoformulations. Solubility evaluation of the drug in various solid and liquid lipids yielded suitability of Compritol 888 and Maisine 35–1. Factor screening study was performed using Plackett-Burman design for identifying vital product and process parameters influencing the critical quality attributes of nanocarriers. Factor optimization study was carried out using Box-Behnken design, thus evaluating the NLCs for particle size, zeta potential, entrapment efficiency and in vitro drug release characteristics. The optimized nanostructured lipidic carriers were evaluated on Caco-2 cells and macrophages indicated significant improvement in the cytotoxicity and uptake performance. In vivo pharmacokinetic evaluation in rats indicated 4.8-fold and 16.5-fold increase in peak plasma concentration and area under curve from lopinavir nanostructured lipidic carriers vis-à-vis plain lopinavir, along with 2.8-fold improvement in the brain biodistribution potential. The above studies corroborated remarkable potential of the nanostructured lipidic carriers as novel drug carriers to reduce virus load in brain as major sanctuary site, thus ameliorating the neurocognitive functions.