SBIR Phase I: Feasibility of a Vaginal Ring for Delivery of Protein Drugs in HIV Prevention

This Small Business Innovation Research (SBIR) Phase I project concerns a major health concern both here in the US and abroad. Currently, no long-term vaginal delivery device is available for the delivery of proteins such as are being investigated for HIV prevention. Our long-term goal is to prevent person-to-person HIV transmission through the use of a vaginal drug delivery ring comparable to other products currently used only for contraception. The objective of this proposal is to develop a proof-of-concept prototype vaginal ring made to demonstrate the dosage levels of the protein 5P12 RANTES, which can be delivered using a ring device. The central hypothesis is that affinity-based interactions can be used to control release of 5P12 RANTES from a vaginal ring, capable of offering protection from HIV infections for 3 weeks and beyond. This work will be accomplished in two aims:1) Fabrication of affinity-based 5P12 RANTES releasing vaginal ring; and 2) Evaluation of 5P12 RANTES release and biological activity in vitro using a receptor blocking assay on human T-cells. The broader impact/commercial potential of this project is tremendous. The spread of human immunodeficiency virus (HIV) is an epidemic with a global infection rate of around 2.5 million per year. One of the strategies being implemented to slow this epidemic is preventing person-to-person transmissions through the use of topical preventative agents applied to the genital mucosa before intercourse. Small molecule drugs such as dapivirine and tenofovir are currently in pre-clinical and clinical trials through application of vaginal gels or insertion of vaginal rings. The major limitation of small molecule drugs is their susceptibility to developing viral resistance. 5P12 RANTES is a protein shown to prevent HIV entry, is remarkably impervious to drug resistance, and is being investigated for local vaginal delivery. Upon proving feasibility, we believe it possible to create a combination vaginal ring that would provide contraceptive or replacement hormone therapy and also protect against vaginal HIV transmission. Future versions of the ring could deliver other protein therapeutics such as vaccines and therapies against HPV.