A novel antioxidant delivery system, Pro-NP™, for protection against UV-related skin cancer

一种新型抗氧化剂输送系统 Pro-NP™，可预防与紫外线相关的皮肤癌

• 批准号: 10258423
• 负责人: Gary Leonard Madsen
• 金额: $ 26.12万
• 依托单位: PROTRANSIT NANOTHERAPY, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10258423
• 关键词: Affect; American; Antioxidants; Biological; Case Study; Catalysis; Collagen; Collagen Fiber; Cutaneous; DNA Damage; Data; Defense Mechanisms; Dermatologic; Development; Dose; Drug Delivery Systems; Ear; Elastin; Elastin Fiber; Enzymes; Epidermis; Event; Excision; Exposure to; Family suidae; Fiber; Formulation; Gene Mutation; Generations; Goals; Half-Life; Hour; Human; Human Volunteers; Incidence; Inflammation; Ions; Lipid Peroxidation; Malignant Neoplasms; Modeling; Mus; Nanotechnology; Oncogenic; Oxidative Stress; Plants; Polymers; Prevention; Production; Proteins; Reactive Inhibition; Reactive Oxygen Species; Risk; Signal Pathway; Skin; Skin Cancer; Skin Care; Skin Neoplasms; Sun Exposure; Sunscreening Agents; Superoxide Dismutase; System; Therapeutic; Topical application; UV Radiation Exposure; UV induced; UV induced DNA damage; Ultraviolet Rays; United States; Vitamins; antioxidant enzyme; base; catalase; cell injury; combat; comparative efficacy; compare effectiveness; innovation; keratinocyte; metal chelator; nanoformulation; nanoparticle; nanoparticle drug; next generation; novel; oxidative damage; prevent; skin damage; skin organogenesis; tanning booths; titanium dioxide; tumorigenesis; ultraviolet

ABSTRACT This project aims to develop a skincare product to prevent ultraviolet (UV)-induced skin cancer with a novel antioxidant delivery system, Pro-NP™, for topical application alone or as an additive to commercial sunblock. Skin cancer is more common than all other cancers combined and affects millions of Americans every year. UV exposure from the sun or tanning beds causes the production of reactive oxygen species (ROS), which overwhelms the skin’s natural antioxidant defense and leads to oxidative stress, photoaging, and skin cancer. While commercial sunscreens can reduce the risk of developing skin cancer, they are poor at blocking UV-A rays responsible for most of the cutaneous ROS production. The topical application of exogenous antioxidants could potentially combat UV generated ROS; however, in their native state, many antioxidants are too unstable to absorb to the deeper layers of the skin effectively. The natural defense system of the skin against UV-induced oxidative stress includes antioxidants superoxide dismutase (SOD) and catalase (CAT), essential enzymes that neutralize the detrimental effects of ROS. Unfortunately, the catalytic activity of native SOD and CAT are short- lived and rapidly cleared, a limiting factor on current therapeutic strategies based on exogenous delivery. ProTransit has developed a proprietary antioxidant delivery system, Pro-NP™, specially formulated for the slow- sustained release of SOD and CAT, to overcome the limitation of the antioxidant’s short half-life. The development of our dermatological product capitalizes on the recent advances of nanotechnology to overcome the biological barriers of using antioxidants to counteract skin damage caused by ROS. Our preliminary studies are promising and demonstrate that Pro-NP is non-toxic in humans and penetrates to the deepest layers of the skin to release active SOD and CAT, reduces DNA damage after UV exposure, and prevents the degradation of essential skin protein fibers like elastin and collagen. The overall objective of this study is to optimize the formulation of plant-based SOD and CAT in Pro-NP, determine the window of efficacy, compare the effectiveness of Pro-NP to commercially available sunscreens, and evaluate the potential of co-application of Pro-NP with commercial sunscreens. Our long-term goal is to develop novel, next-generation skincare products for topical application to prevent UV-induced skin damage and ultimately to reduce the incidence of skin cancer.

摘要