Recent advances in long-acting nanoformulations for delivery of antiretroviral drugs

In spite of introduction of combination antiretroviral therapy (cART) against human immunodeficiency virus (HIV) infection; inaccessibility and poor adherence to oral cART costs 10 in 100,000 death worldwide. Failure in adherence leads to viral rebound, emergence of drug resistance and anticipated HIV infection in high risk individuals. Various Long-acting antiretroviral (LA ARV) nanoformulations including nano-prodrug, solid drug nanoparticles (SDN), nanocrystals, aspherical nanoparticles, polymeric and lipidic nanoparticles have shown plasma/tissue drug concentration in the therapeutic range for several weeks during pre-clinical evaluation. LA ARV nanoformulations therefore have replaced cART as better alternative for the treatment of HIV infection. Cabenuva™ is recently approved by Health Canada containing LA cabotegravir+LA rilpivirine nanocrystals (ViiV healthcare) for once monthly administration by intramuscular route. The LA nanoformulation due to its nanosize insist on better stability, delivery to lymphatic, slow release into systemic circulation via lymphatic-circulatory system conjoint and secondary drug depot within infiltered immune cells at site of administration and systemic circulation in contrast to conventional drugs. However, the pharmacokinetic, biodistribution and efficacy of LA nanoformulations hinge onto physicochemical properties of the drugs and route of administration. Therefore, current review emphasizes on these contradistinctive factors that affects the reproducibility, safety, efficacy and toxicity of LA anti-HIV nanoformulations. Moreover, it expatiates on application of profuse nanoformulations for long-acting effect with promising preclinical discoveries and two clinical leads. To add on, utilization of physiology-based and mechanism-based pharmacokinetic modelling and in vivo animal models which could lead to enhanced safety and efficacy of LA ARV nanoformulations in humans have been included.