A Review of Current Intravaginal Drug Delivery Approaches Employed for the Prophylaxis of HIV/AIDS and Prevention of Sexually Transmitted Infections

Abstract

Abstract. The objective of this review is to describe the current status of several intravaginal anti-HIV microbicidal delivery systems these delivery systems and microbicidal compounds in the context of their stage within clinical trials and their potential cervicovaginal defence successes. The global Human Immuno-Deficiency Virus (HIV) pandemic continues to spread at a rate of more than 15,000 new infections daily and sexually transmitted infections (STIs) can predispose people to acquiring HIV infection. Male-to-female transmission is eight times more likely to occur than female-to-male transmission due to the anatomical structure of the vagina as well as socio-economic factors and the disempowerment of women that renders them unable to refuse unsafe sexual practices in some communities. The increased incidence of HIV in women has identified the urgent need for efficacious and safe intravaginal delivery of anti-HIV agents that can be used and controlled by women. To meet this challenge, several intravaginal anti-HIV microbicidal delivery systems are in the process of been developed. The outcomes of three main categories are discussed in this review: namely, dual-function polymeric systems, non-polymeric systems and nanotechnology-based systems. These delivery systems include formulations that modify the genital environment (e.g. polyacrylic acid gels and lactobacillus gels), surfactants (e.g. sodium lauryl sulfate), polyanionic therapeutic polymers (e.g. carageenan and carbomer/lactic acid gels), proteins (e.g. cyanovirin-N, monoclonal antibodies and thromspondin-1 peptides), protease inhibitors and other molecules (e.g. dendrimer based-gels and the molecular condom). Intravaginal microbicide delivery systems are providing a new option for preventing the transmission of STIs and HIV.

Designed oligomers of cyanovirin-N show enhanced HIV neutralization

“…This property is promising for the development of these or other variants for therapeutic use, as they can potentially be used throughout the world. Because of the increase in potency relative to WT CV-N, CVN 2 L0 could be more effective in any prophylactic treatment protocol that WT CV-N is currently being investigated for, including gels, suppositories, and in vivo Lactobacillus delivery (36,37). In addition to the increase in potency of CVN 2 L0, the lack of a proteolytically sensitive linker between the CV-N repeats suggests that this variant will probably have similar stability in vivo as WT CV-N. CVN 2 L0 shows similar potency to many of the broadly neutralizing antibodies that have recently been reported but is easier to express than intact antibodies and therefore could be used for a range of therapeutics that are intractable for antibodies.…”

The antiviral protein cyanovirin-N: the current state of its production and applications

“…For example, the 50% inhibitory concentration of this lactobacillus-derived CVN to CCR5-tropic HIV BaL is only 0.3 nM (Liu et al 2006). The development of a novel, live microbicide that employs a commensal bacteria to deliver CVN to the vaginal channel is another fascinating application of CVN (Ndesendo et al 2008). …”

Sensitive and Rapid HPLC Quantification of Tenofovir from Hyaluronic Acid-Based Nanomedicine

“…Microbicides are currently the principal focus for HIV prevention strategies (4,5). These are the agents used topically within the vagina or rectum in order to prevent infections caused by HIV and other enveloped viruses and sexually transmitted pathogens.…”