Human Immunodeficiency Virus Type 1 (HIV-1) remains one of the leading causes of death worldwide. Present combination antiretroviral therapy has substantially improved HIV-1 related pathology. However, delivery of therapeutic agents to the HIV reservoir organ like Central nervous system (CNS) remains a major challenge primarily due to the ineffective transmigration of drugs through Blood Brain Barrier (BBB). The recent advent of nanomedicine-based drug delivery has stimulated the development of innovative systems for drug delivery. In this regard, particular focus has been given to nanodiamond due to its natural biocompatibility and non-toxic nature–making it a more efficient drug carrier than other carbon-based materials. Considering its potential and importance, we have characterized unmodified and surface-modified (-COOH and -NH2) nanodiamond for its capacity to load the anti-HIV-1 drug efavirenz and cytotoxicity, in vitro. Overall, our study has established that unmodified nanodiamond conjugated drug formulation has significantly higher drug loading capacity than surface-modified nanodiamond with minimum toxicity. Further, this nanodrug formulation was characterized by its drug dissolution profile, transmigration through the BBB, and its therapeutic efficacy. The present biological characterizations provide a foundation for further study of in-vivo pharmacokinetics and pharmacodynamics of nanodiamond-based anti-HIV drugs.

Since its discovery almost three decades ago, HIV-1 has grown into the most aggressive pandemic of modern time. Following the implementation of combination antiretroviral therapy, the pathological outcome of HIV infection has substantially improved. However, combination antiretroviral therapy is limited by several factors including, long-term toxicity, serious side effects and complex dosing regimens, and so on. In this regard, researchers have directed their attention toward enhancing current treatment strategies and/or developing alternative HIV-1 therapeutics. In recent years, this attention has fixated on nanomedicine-based anti-HIV therapeutics (HIV-1 nanotherapeutics). In the present study, we have reviewed several HIV-1 nanotherapeutics that have shown success at the preclinical level and/or Phase I/II clinical trials. We also discuss the possible benefits of these nanomedicine-based approaches and their future outlook.

Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9) have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function, and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.

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