Core--Drug Development

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DESCRIPTION (provided by applicant): Molecularly targeted agents against 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 I-III and clinical trials in Project IV cannot be initiated without the preparation and proper testing of well-characterized, stable formulations of topical agents. The Drug Development Core provides this crucial service to the Program Project. The objective of the 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. An innovative addition to this competing application is the ability and expertise to synthesize chemical entities as prodrugs in order to enhance 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 clinicalgrade supply for human trials in Project IV. The Drug Development 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 Drug Development Core will work closely with each Project to provide necessary and appropriate 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.