Biological Optimization of Polymer-Based Antiretroviral Drug Towards the Gut-Associated Lymphoid Tissue (GALT)

Background: Combination antiretroviral therapy (cART) has significantly decreased the disease mortality associated with HIV-1 but does not efficiently reach the HIV reservoir organs such as GALT. In this regard, the present study determined the efficacy of the polymer-based nanoformulations using F127 alone and in combination with L61 to encapsulate three clinically available cART drugs such as Emtricitabine (FTC), Tenofovir Disoproxil Fumarate (TDF), and Dolutegravir (DTG) in in vitro and in vivo system. Methods: The selected formulations were studied for their biological and chemical characterization towards human cell line viz. Caco-2 and Human peripheral blood mononuclear cells (PBMC) and in vivo mouse model. Results: The majority of the nanoformulations were observed to be in the size range of the nanoparticle. The safety study of all these formulations indicated that the combination of F127 + L61 formulations showed no significant toxicity, improved drug release properties in Caco 2, PBMC and in vitro Mcell model. The study has established a sustained release of the F127 + L61 nanoformulations for a period of 14 days in in vitro and in vivo models. Conclusions: The overall study proved that the combination of polymer-based formulations has potential applications in improving HIV-1 treatment with far fewer side effects compared to current therapy