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

摘要 本项目旨在开发一种新的皮肤护理产品，以预防紫外线（UV）引起的皮肤癌。 抗氧化剂递送系统，Pro-NP ™，用于单独局部应用或作为商业防晒霜的添加剂。 皮肤癌比所有其他癌症加起来更常见，每年影响数百万美国人。UV 暴露于阳光或晒黑床会导致活性氧（ROS）的产生， 破坏皮肤的天然抗氧化防御，导致氧化应激，光老化和皮肤癌。 虽然商业防晒霜可以降低患皮肤癌的风险，但它们在阻挡UV-A方面很差 射线负责大部分皮肤ROS的产生。外用外源性抗氧化剂 可以潜在地对抗紫外线产生的ROS;然而，在其天然状态下，许多抗氧化剂太不稳定 有效地吸收到皮肤的深层。皮肤对紫外线诱导的自然防御系统 氧化应激包括抗氧化剂超氧化物歧化酶（SOD）和过氧化氢酶（CAT），它们是 中和活性氧的有害影响。不幸的是，天然SOD和CAT的催化活性较低- 存活并迅速清除，这是目前基于外源性递送的治疗策略的限制因素。 ProTransit开发了一种专有的抗氧化剂输送系统Pro-NP ™，专门为缓慢的 持续释放SOD和CAT，克服抗氧化剂半衰期短的限制。的 我们的皮肤科产品的开发利用了纳米技术的最新进展， 使用抗氧化剂抵消活性氧引起的皮肤损伤的生物屏障。我们的初步研究 是有希望的，并证明Pro-NP β-内酰胺酶是无毒的，在人类和渗透到最深的层， 皮肤释放活性SOD和CAT，减少紫外线暴露后的DNA损伤，防止降解 弹性蛋白和胶原蛋白等重要的皮肤蛋白纤维。本研究的总体目标是优化 配方植物为基础的SOD和CAT在Pro-NP酶，确定窗口的功效，比较 Pro-NP的有效性，商业上可获得的防晒霜，并评估共同应用的潜力， Pro-NP防晒霜与商业防晒霜。我们的长期目标是开发新颖的下一代护肤品 产品用于局部应用，以防止紫外线引起的皮肤损伤，并最终减少 皮肤癌

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.