Nonclinical Laboratory Studies: Microbicide Formulation and Delivery
Population Council laboratory scientists are developing vaginal rings and water-based gels to deliver microbicide formulations.
Laboratory scientists at the Population Council's Center for Biomedical Research are developing safe, effective, and acceptable microbicides to prevent acquisition and transmission of HIV and other sexually transmitted infections, such as herpes.
The microbicides contain one or more antiviral agents formulated either as extended-release vaginal rings or water-based gels for use in the rectum or vagina. In either case, the microbicide must be carefully formulated and manufactured to ensure that the active agents are available to block infection.
Based on commercially available products, the Council’s vaginal rings are made of either silicone rubber or a plastic material called EVA. They release MIV-150, a highly water-insoluble enzyme inhibitor that prevents infected cells from producing new virus for up two months. This prolonged release of MIV-150 might provide continuous protection against HIV infection.
The Council’s water-based microbicide gels typically contain MIV-150 and a natural polymer called carrageenan. Carrageenan is extracted from seaweed and gives the gels a number of desirable properties: It thickens the gels so they remain in the vagina during normal activities and during coitus and also keeps the active agents suspended in the gel, so they don’t settle during storage, ensuring that every dose of gel contains the correct amount of MIV-150. Carrageenan gels also have a smooth, silky feel that enhances sexual pleasure for many people.
Council scientists are working to optimize delivery of MIV-150 to target cells and tissues. They are using state-of-the art drug-delivery systems such as MIV-150/sugar complexes and nanoparticles (microscopic polymer balls loaded with MIV-150) to improve the efficacy of PC-815.
They also are preparing microbicide gels in which the carrageenan is replaced with other natural and man-made polymers. These gels might have interesting properties in terms of spectrum of activity and movement within the rectum and vagina.
A single dose of a MIV-150/zinc acetate gel provides 24 h of protection against vaginal simian human immunodeficiency virus reverse transcriptase infection, with more limited protection rectally 8-24 h after gel use (abstract) (HTML)
Kenney,Jessica; Singer,Rachel; Derby,Nina R.; Aravantinou,Meropi; Abraham,Ciby J.; Menon,Radhika; Seidor,Samantha; Zhang,Shimin; Gettie,Agegnehu; Blanchard,James; Piatak Jr.,Michael; Lifson,Jeffrey D.; Fernandez-Romero,Jose A.; Zydowsky,Thomas M.; Robbiani,Melissa
AIDS Research and Human Retroviruses 28(11): 1476-1484
Publication date: 2012
The nonnucleoside reverse transcription inhibitor MIV-160 delivered from an intravaginal ring, but not from a carrageenan gel, protects against simian/human immunodeficiency virus-RT infection (abstract) (PDF)
Aravantinou,Meropi; Singer,Rachel; Derby,Nina R.; Calenda,Giulia; Mawson,Paul; Abraham,Ciby J.; Menon,Radhika; Seidor,Samantha; Goldman,Daniel; Kenney,Jessica; Villegas,Guillermo; Gettie,Agegnehu; Blanchard,James; Lifson,Jeffrey D.; Piatak Jr.,Michael; Fernandez-Romero,Jose A.; Zydowsky,Thomas M.; Teleshova,Natalia; Robbiani,Melissa
AIDS Research and Human Retroviruses 28(11): 1467-1475
Publication date: 2012
Zinc acetate/carrageenan gels exhibit potent activity in vivo against high dose HSV-2 vaginal and rectal challenge (abstract)
Fernandez-Romero,Jose A.; Abraham,Ciby J.; Rodriguez,Aixa; Kizima,Larisa; Jean-Pierre,Ninochka; Menon,Radhika; Begay,Othell; Seidor,Samantha; Ford,Brian E.; Gil,Pedro I.; Peters,Jennifer; Katz,David; Robbiani,Melissa; Zydowsky,Thomas M.
Antimicrobial Agents and Chemotherapy 56(1): 358-368
Publication date: 2012
The nonnucleoside reverse transcriptase inhibitor MIV-150 in carrageenan gel prevents rectal transmission of simian/human immunodeficiency virus infection in macaques (abstract)
Singer,Rachel; Derby,Nina R.; Rodriguez,Aixa; Kizima,Larisa; Kenney,Jessica; Aravantinou,Meropi; Chudolij,Anne; Gettie,Agegnehu; Blanchard,James; Lifson,Jeffrey D.; Piatak Jr.,Michael; Fernandez-Romero,Jose A.; Zydowsky,Thomas M.; Robbiani,Melissa
Journal of Virology 85(11): 5504-5512
Publication date: 2011
Project Stats
Location: United States
Program(s):
HIV and AIDS
Topic(s):
HIV biomedical research
Microbicides
Duration: 1/2004 - ongoing
Population Council researchers:
Melissa Robbiani
José Romero
Natalia Teleshova
Thomas Zydowsky
Non-Council collaborators:
David Katz (Duke University)
Lisa Rohan (University of Pittsburgh)
Donors:
National Institutes of Health
Swedish International Development Cooperation Agency
Swedish Ministry for Foreign Affairs
US Agency for International Development
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