Directing the Antiretroviral Drugs to the Brain Reservoir: A Nanoformulation Approach for NeuroAIDS.

BACKGROUND: Human immunodeficiency virus (HIV)/AIDS is one of the principal concerns contributing to the global burden and the accompanying deleterious outcomes could not be left unattended. Despite significant advances and innovative research being conducted throughout the globe in order to improve the therapeutic profile of conventionally available antiretroviral (ARV) drugs in the eradication of HIV virus reservoirs, its penetration across the blood-brain barrier (BBB) is still a formidable mission. This makes the central nervous system a dominant and vulnerable site for virus propagation, which ultimately affects the therapeutic potential of the drug administered. Therefore there is an upsurge in the prerequisite of novel technologies to come into play, paving the way for nanotechnology. METHODS: This review primarily provides a comprehensive outline and emphasizes on the nanotechnological techniques employed for the delivery of ARV drugs and their stupendous advantages in overcoming the hurdles associated with the same. RESULTS: The nanotechnological approach bears the potential of site-specific delivery across the BBB via targeting explicit transport processes and provides a sustained release mechanism. Furthermore, different routes of administration explored have also yielded beneficial outcomes for the delivery of ARV drugs. CONCLUSION: The futuristic holistic nanotechnology methods, however, should focus on increasing drug trafficking and permeability across the BBB to ameliorate the therapeutic effect of ARV drugs. Additionally, the domain warrants clinical studies to be undertaken to make the technology commercially viable and a success to deal with the problems of the treatment strategy.

The Yin and Yang of Antiviral Innate Immunity in Central Nervous System.

The innate immune system provides protection against invading neurotropic viruses. It acts as the first line of defense against invading viruses and plays an elementary role in their pathogenesis. The list of viruses capable of infecting human central nervous system (CNS) is quite long, most important of them are Japanese Encephalitis virus (JEV), rabies virus, West Nile virus (WNV), herpes simplex virus (HSV), St. Louis encephalitis virus (SLEV), La Crosse virus, tick borne encephalitis virus (TEBE) and polio virus. Germ line pattern recognition receptors (PRRs) such as Toll like receptors (TLRs), nucleotide binding oligomerization domain (NOD) - like receptors (NLRs), retinoic acid-inducible gene I (RIG-I) -like helicases or RIG-I-like receptors (RLRs) and cytosolic DNA sensors recognize the pathogen associated molecular patterns (PAMPs) and initiate an immune response against invading pathogen. Although PRRs were originally characterized in peripheral immune cells but accumulating evidence also suggest their crucial roles in CNS to combat against neurotropic viruses. In this review, we will highlight the recent developments in our understating of the mechanisms by which PRRs in resident brain cells provide protection against invading neurotropic viruses.

HIV Preclinical-Clinical Therapeutics Research: central nervous system approaches.

The prevalence of HIV-associated brain disorders is reportedly increasing due, in part, to the prolonged life span of individuals who are surviving well on highly active antiretroviral treatments (HAART). While clinicians report CNS-related deficits that are more subtle in presentation than the frank dementia evident in the pre-HAART era, the milder presentation continues to substantively reduce an individual's quality of life. The development of novel drugs or therapeutic strategies for treating HIV-related CNS disease is important as most investigators agree that the brain is a sanctuary for latent virus, local viral recrudescence, and associated brain inflammatory responses. The prolonged chronic and cumulative effects on the brain of living with HIV-related inflammatory processes, antiretroviral treatments, and their long-term side effects, toxicities, and brain-related aging processes collectively indicate that the burden of CNS and PNS complications will increase profoundly during the upcoming years. Considering the high expense for new drugs entering CNS-related clinical trials and their ultimately low success rate, the NIMH convened a meeting entitled, HIV Preclinical-Clinical Therapeutics Research Meeting, to discuss the current and proposed novel approaches for neuroAIDS drug development and clinical practices. The purposes of the meeting were twofold: to identify the most promising approaches for future neuroAIDS therapeutics development research and to discuss optimal structures and partnerships with industry that may facilitate the successful movement of compounds from the bench to the bedside. Several themes can be derived from the sessions and are highlighted below for preclinical, translational and clinical neuroAIDS therapeutics research.