The overall objective of this program is to commercially develop a novel nystatin (NYST) Releasing System for HIV and Candida infected patients which is superior to the currently marketed orally administered antifungal products in that it does not rely on patient compliance for effectiveness in preventing the development of oral candiasis. The broad objectives of this Phase I proposal are to demonstrate the technical feasibility of preparing 3-5,000 controlled release nystatin (NYST) devices per batch with 0 mg/day, 0.4 mg/day and 2.0 mg/day of NYST-release rates that provides continuous protection against Candida overgrowth for twenty days to three months, easily replaceable by a trained health giver and which does not depend on patients compliance for effectiveness. Specific objectives are to characterize the NYST-devices for drug content, uniformity of dosage, kinetics of NYST release and determine the bioactivity of the released NYST to inhibit the proliferation of yeast associated with oral candidosis by employing in- vitro test systems. If the results are promising, continue the NYST-product development, determine the long-term usage (chronic) toxicity in appropriate animal models, assemble the generated information into an Investigational New Drug (IND) application and file with the Food and Drug Administration (FDA) for the initiation of safety and efficacy (Phase I and II clinical studies), as part of the Phase II SBIR program.Proposed commercial application:The NYST-System is professionally applied and the NYST reservoir is programmed to release low quantities of NYST at a steady rate for 20 days to 3 months duration. It is a passive device and does not depend on patient compliance for efficacy. It is ideally-suited for immunocompromized HIV and elderly patients who are unable to practice rigorous daily oral rinsing with a NYST solution to prevent the overgrowth of yeast.National Institute of Allergy and Infectious Diseases (NIAID)
