The primary objective of this Core will be to formulate cyanovirin (CV-N) into gel- and cream-based vaginal delivery systems. Since little is known regarding the physical function of vaginal dosage forms, the Core will support the proposed study of deployment by initially developing and supplying placebo formulations. These physical assessments of formulations and deployment will allow formulation development to proceed while recombinant CV-N production is being developed. Gel and cream formulations with a range of physical properties will be prepared and evaluated for spreading and coating properties in vitro, and for vaginal coating in vivo. These evaluations will provide feedback information for formulation optimization. CV-N will then be incorporated into optimized gel and cream formulations and tested in vitro for stability and drug release using standard pharmaceutical methods, and for biological activity. This evaluation will allow for advanced formulation optimization regarding biological activity. A variety of antimicrobial agents (e.g., C31G, defensins) and additional antiviral agents (e.g., UC781) will be incorporated into optimized CV-N gels and creams and evaluated using the same iterative optimization processes, leading to the availability of formulated combinations of microbicides. Analytical methods of determining CV-N (and other compounds) levels in formulations and in biological fluids will be developed as needed. Lastly, the Core will be responsible distributing CV-N (neat and formulated) to the other projects and cores.
