Moleculariy targeted agents against solar UV signal transduction pathways can be incorporated into topical formulations engineered to optimize delivery to skin and maximize the probability of success in preclinical and clinical evaluation. Long-term preclinical carcinogenesis studies in Projects 1-2 and dinical trials in Project 3 cannot be initiated without the preparation and proper testing of well-characterized, stable formulations of topical agents. The objective ofthe Drug Development Core is to efficiently design, prepare, test, and provide pharmaceutically suitable topical formulations of new skin cancer chemopreventive agents to Program Project investigators and to provide regulatory support for clinical development of candidates that show promise. Additionaly, the core provides the ability and expertise to synthesize new chemical entities as prodrugs or analogues in order to manipulate solubility, absorption, and delivery to the epidermis. This objective will be accomplished by the following Specific Aims: 1) To prepare stable formulations of promising new agents that can be effectively delivered to the epidermis following topical application, 2) To prepare batch formulations for long-term carcinogenesis studies in vivo and perform necessary preclinical toxicology, pharmacokinetic, and stability studies, and 3) To coordinate and prepare Investigational New Drug (IND) applications for FDA approval, and supervise production and distribution of clinical-grade supply for human trials in Project 3. The Core will oversee all aspects of topical agent preparation, formulation, and supply for each of the Projects. Quality control and assurance methods developed by the Drug Development Core in consultation with the Biometry Core will ensure regulatory compliance and enhance efficiency. The Core will work closely with each Project to provide necessary and appropriate preformualtion and topical formulations for each stage of mechanistic and efficacy studies in vivo. This will allow us to circumvent problems with epidermal delivery that normally hinder development of otherwise promising topical agents, and optimize the crucial selection criteria for advancement of new agents to clinical testing. This will greatly enhance our ability to translate basic science discoveries into new skin cancer chemopreventive drugs. This highly interactive and clinically translational research progrann project focuses on the successful preclinical testing of targeted chemoprevention agents in innovative mouse models (Projects 1 and 2) followed by the design and implementation of clinical trials in at risk human populations (Project 3). Detailed descriptions ofthe decision-tree selection process as well as the interactions between Projects and Cores are found on the Resources Format Page.
The Drug Development Core will provide the required topical formulation, safety and regulatory activities necessary to translate the active chemical entities identified from the basic science Projects 1 and 2 into clinical studies developed and performed by Project 3.
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