The goal of this revised Phase 1 proposal remains to identify and initiate the pharmaceutical development of a topical formulation ingredient capable of reducing the risk associated with dermal and systemic exposure to hazardous materials (i.e., a permeation retarder). The strategy is to select a lead chemical entity from several candidate molecules designed to interact with the stratum comeum so that it becomes less permeable to toxic agents. The selection of an effective skin permeation retarder will be based upon its ability to reduce the skin absorption of a variety of hazardous materials, be substantive to skin such that it will be active for prolonged periods of time, and show essentially no dermal toxicity. In Phase I of this project we intend to synthesize and evaluate in vitro the permeation retardant efficacy of several potential retarder candidates, perform primary dermal and acute oral toxicity analysis in animals of a lead and back-up candidate, and perform formulation studies that will generate prototype products. In Phase II we will seek to scale-up the synthesis of the lead compound, optimize potential formulations, determine long-term chemical, microbiological and physical stability, and complete safety and efficacy studies as required by the FDA.
Thesaurus Terms: chemical structure function, drug design /synthesis /production, inhibitor /antagonist, membrane permeability, skin absorption, topical drug application, transdermal drug delivery drug adverse effect, keratinocyte, skin pharmacology, toxicology clinical research, human tissue, laboratory rabbit, laboratory rat
