Development and testing of a silibin-containing sunscreen

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DESCRIPTION (provided by applicant): We propose to develop a cosmetic sunscreen formulation Sunsil, containing silibin which has been demonstrated to have anti-cancer effects. There is a global increase in skin cancer as humans have more and more leisure time and alter both their lifestyles and clothing choices. We have accumulated data in cell culture and in mouse models that reveal silibin to be a potent anti-neoplastic agent with a very favorable therapeutic index; it is likely that silibin can reverse or slow the development of skin cancer via its complex pleitropic effects on signal transduction and cell cycle regulation. Commercialization of this agent as a novel sunscreen lotion will depend on further formulation efforts, preclinical data generation, and ultimately a large international trial in high-risk patients such as the transplant population. We believe the opportunity for Sunsil is obvious among the organ transplant community, but given the more general population's interest in effective sunscreen products, we believe Sunsil has significant potential of capturing market share among a much broader audience. Conservatively, because of the uniqueness of Sunsil in that it fulfills a specific unmet need, we believe Sunsil can capture 5% of the worldwide sunscreen market, or approximately 20 million dollars in sales, within the 5-year window following full product launch. While silibin is a "natural" product derived from milk thistle extract, the formulation we work with is pure, and its biology and mechanism of action is well understood at the basic science level. We at UCDHSC have the only Phase I trial we are aware of examining safety and dosage of Silybin-PhytosomeTM in prostate cancer patients, and we are about to commence two different Phase II studies as detailed below in preliminary studies section. Our detailed human pharmacokinetic data on free and conjugated silibin levels in blood and urine, some of which is presented herein, and our extensive studies on silibin's mechanisms of action, uniquely situates us to perform the studies described here. The specific aims of this proposal are to: (1) Prepare candidate Sunsil formulations in cyclodextrin base with and without UV blockers; (2) Test candidate Sunsil formulations in SKH1 hairless mice for biological effects against acute, single UVB radiation-induced DNA damage and alterations in p53 status, proliferation and apoptosis; and (3) Perform tumorigenesis studies in SKH1 hairless mice using the best Sunsil formulation as identified in aim 2.