SBIR-STTR Award

The skin plays multiple roles in protection from environmental insults. A growing body of evidence demonstrates that micronutrients including vitamins B6, B12, C, E, folate, and niacin are involved in the maintenance of genomic integrity of skin cells via mechanisms ranging from scavenging ROS to the repair of DNA damage. Sub-clinical micronutrient deficiencies are prevalent even in advanced societies and micronutrient status decreases with age. The above information leads to the hypothesis that improvement of the micronutrient status of skin will retard skin deterioration by enhancement of cellular defense mechanisms to environmental insults. The overall objective of this proposal is to determine the feasibility of developing a topical micronutrient delivery system to provide nutritional support to skin. The specific aims of the proposed research are (i) to synthesize and characterize a series of micronutrient derivatives (pronutrients) designed to effectively diffuse through the stratum corneum layer of skin, (ii) to determine the optimal lipophilicity of pronutrients for topical delivery to the cellular components of skin, (iii) to develop inactive companion co-esters for the purpose of regulating micronutrient delivery, and (iv) to determine the efficacy of co-ester companions in the delivery of nutrients to specific areas of skin. PROPOSED COMMERCIAL APPLICATION: Biomedical research of the past 20 years has shown that the health of skin, like other aspects of human health, requires nutritional support. Benefiting the health of skin via novel pronutrients and a novel formulation strategy that can be patent protected has considerable commercial potential in a skin care market that exceeds $20 billion per year. Further, this market promises to coninue to grow as the population continues to age and migrate to the sun belt.

Skin damage represents a major public health problem. For example, endstage skin damage in the form of non-melanoma skin cancers are the most frequently diagnosed malignancies in the USA. The occurrence of DNA damage and cellular responses to DNA damage are major factors in skin pathologies, including skin cancer. A compelling body of evidence now indicates that there are therapeutic candidates for skin damage prevention. However, a major challenge for the development of prevention strategies for skin damage relates to the difficulty of delivering micronutrients to skin. In research completed under Phase I, it was demonstrated that topical delivery of micronutrients to skin cells is feasible and that such delivery provides prevention benefit. This is a Phase II SBIR application to develop technology for delivering specific micronutrients to skin cells to prevent skin damage and potentially skin cancer. The proposed research will test the hypotheses that a strategy employing micronutrients to limit skin damage by multiple mechanisms for preventing DNA damage, enhancing DNA repair, preventing immune suppression, and preventing migration of transformed cells from epidermis to dermis will limit skin damage including skin cancer and that topical delivery of key micronutrients to skin cells represents the most efficacious approach for prevention of skin damage and that delivery can be achieved by the development of pronutrients specifically tailored for targeted delivery to skin. The specific aims of this proposal are to design, synthesize, characterize and evaluate the topical delivery properties of specific pronutrients (niacin, vitamin E, folate, Q1O, and lipoate) to evaluate the safety, tolerance, and efficacy, singly and in combinations of pronutrients having optimal delivery properties in a mouse model. The efficacy of delivery of the lead candidate for each pronutrient determined in the mouse model will be evaluated in the porcine model, the most predictive animal model of human skin. The successful completion of these objectives will complete early phase commercial development of technology intended to translate to a product that will allow optimization of skin health and prevent skin damage, including skin cancer.

Thesaurus Terms:
chemoprevention, drug design /synthesis /production, folate, prodrug, short chain fatty acid, therapy design /development, tocopherol, topical drug application, ubiquinone DNA damage, DNA repair, biomarker, cell migration, combination chemotherapy, drug screening /evaluation, hydropathy, immunosuppression, keratinocyte, skin neoplasm, ultraviolet radiation computer simulation, hairless mouse, miniature swine