Development of a liposome microbicide formulation for vaginal delivery of octylglycerol for HIV prevention

Abstract

The feasibility of using a liposome drug delivery system to formulate octylglycerol (OG) as a vaginal microbicide product was explored. A liposome formulation was developed containing 1% OG and phosphatidyl choline in a ratio that demonstrated in vitro activity against Neisseria gonorrhoeae, HSV-1, HSV-2 and HIV-1 while sparing the innate vaginal flora, Lactobacillus. Two conventional gel formulations were prepared for comparison. The OG liposome formulation with the appropriate OG/lipid ratio and dosing level had greater efficacy than either conventional gel formulation and maintained this efficacy for at least 2 months. No toxicity was observed for the liposome formulation in ex vivo testing in a human ectocervical tissue model or in vivo testing in the macaque safety model. Furthermore, minimal toxicity was observed to lactobacilli in vitro or in vivo safety testing. The OG liposome formulation offers a promising microbicide product with efficacy against HSV, HIV and N. gonorrhoeae.

Nanoparticle-based drug delivery to the vagina: A review

“…Wang et al formulated another novel candidate microbicide with low water solubility, octylglycerol, in phosphatidylcholine liposomes for vaginal application [94]. In comparison to water-based Carobopol or poloxamer hydrogel formulations with glycerin as a solubilizing agent for octylglycerol, after 2 months of storage, octylglycerol liposomes had better in vitro activity against HSV-1, HSV-2, and HIV-1, presumably due to increased product stability.…”

“…Formulation of octylglycerol into liposomes increased the minimum cidal concentration (MCC) of octylglycerol to lactobacillus, but the lipid/octylglycerol ratio had to be carefully controlled to avoid significant killing, measured as >4-log reduction in Lactobacilli. No signs of toxicity were observed after 2 h exposure of octylgelycerol liposomes to ex vivo human cervical tissue [94]. …”

Nanomedicine for Infectious Disease Applications: Innovation towards Broad‐Spectrum Treatment of Viral Infections

“…Liposome drug delivery systems are among the most clinically advanced nanomedicines and offer a possible nanomedicine strategy that could be incorporated into viral treatment strategies to improve the therapeutic properties of antiviral drugs. One example of this kind is the development of a liposome microbicide formulation for vaginal delivery of octylglycerol to prevent HIV transmission . This move would be a natural extension of ongoing liposomal applications in cancer therapy, where a wealth of experience with manufacturing and quality control has already been accrued.…”

Preparation and characterization of mucoadhesive nanoparticles of poly (methyl vinyl ether-co-maleic anhydride) containing glycyrrhizic acid intended for vaginal administration

“…Unfortunately, due to its selfcleaning action, conventional preparations often require frequent administrations to ensure a therapeutic dose. To overcome this problem, mucoadhesive systems appear to be highly appropriate to prolong the residence time of a drug in the vaginal cavity [14][15][16][17][18] .…”