“Fusion and binding inhibition” key target for HIV-1 treatment and pre-exposure prophylaxis: targets, drug delivery and nanotechnology approaches

<p>More than 35 million people are living with HIV worldwide with approximately 2.3 million new infections per year. Cascade of events (cell entry, virus replication, assembly and release of newly formed virions) is involved in the HIV-1 transmission process. Every single step offers a potential therapeutic strategy to halt this progression and HIV fusion into the human host cell is one such stage. Controlling the initial event of HIV-1 transmission is the best way to control its dissemination especially when prophylaxis is concerned. Action is required either on the HIV’s or host’s cell surface which is logically more rational when compared with other intracellular acting moieties. Aim of this manuscript is to detail the significance and current strategies to halt this initial step, thus blocking the entry of HIV-1 for further infection. Both HIV-1 and the possible host cell’s receptors/co-receptors are under focus while specifying the targets available for inhibiting this fusion. Current and under investigation moieties are categorized based on their versatile mechanisms. Advanced drug delivery and nanotechnology approaches present a key tool to exploit the therapeutic potential in a boosted way. Current drug delivery and the impact of nanotechnology in potentiating this strategy are detailed.</p

Efaverinz and nano-gold-loaded mannosylated niosomes: a host cell-targeted topical HIV-1 prophylaxis via thermogel system

<p>Sexual dissemination of Human Immunodeficiency Virus-1 (HIV-1) is the prime mode of its spread. Topical microbicidal approach has gained much attention, but no real success is observed till date, either due to toxicity or resistance of active moieties and the lack of efficient drug delivery approaches. In this research protocol, a unique combination approach of a standard drug moiety, that is, Efaverinz (EFV) and a nanometal, that is, gold nanoparticles (GNPs) was tried. Both these candidates were delivered through a mannosylated niosomal system, to exploit protein (lectins present on HIV host cells) – carbohydrate (oligosaccharides such as mannan present on HIV gp-120 receptor) interaction. GNPs (10.4 nm average size) were entrapped inside the aqueous core, whereas lipophilic EFV was loaded in the bilayer membrane. Results demonstrated a significant increase in antiviral activity when EFV was fired with GNPs. Delivery of this combination via mannosylated niosomes proved to be a perfect approach with exceedingly well potential compared to non liganded niosomal system. A thermosensitive gel vehicle was prepared and the loaded niosomes were dispersed in it to have a nanogel system. The optimized formulation was evaluated for its prophylactic activity and the results showed completely inhibited viral dissemination at folds dilution levels.</p