The Development of Inorganic Ultraviolet Filters Exhibiting Improved Topical Retention on Human Skin for The Prevention of Skin Cancer

项目摘要/摘要 该第二阶段项目是基于NCI第一阶段奖1R43CA236265-01，并且是重新提交的。 需要解决的问题和意义：暴露在紫外线辐射(UVR)中是一种危险因素 皮肤癌的发生，卫生保健机构建议使用防晒霜作为预防措施 测量。商业防晒霜的一个主要局限性是需要不断重复使用才能获得充分的好处。 这是因为防晒霜含有紫外线过滤器，与皮肤缺乏亲和力，正常情况下很容易去除。 穿上。具有更好皮肤保留力的耐用滤镜的开发有可能缓解紫外线- 中介毒性，并仍然是一个重要的优先事项。产品和长期目标：Nanometics(d.b.a.博士 Bioscicis[PhD])正在开发新型的二氧化钛和氧化锌紫外线过滤器，这种过滤器包含一种涂层， 与皮肤蛋白质相互作用，提高局部保留时间长达160分钟。新型紫外线滤光器是AS 作为商业紫外线过滤器的光保护和安全，并且很容易用廉价的原料合成。 它们将作为防晒霜和其他局部产品的成分在全球销售。预计这些 紫外线滤清器将减少不断重复使用产品的需要。技术创新：表面上的 商用二氧化钛和氧化锌紫外线过滤器被共价修饰，以包含一种相互作用的涂层 含有皮肤蛋白质，以延长局部保留时间。涂层的设计是为了在皮肤上形成稳定的相互作用 PH值，用肥皂和水清洗就可以很容易地去除。具体目标#1证明 HPGA的改性不影响紫外线滤清器的皮肤穿透轮廓 在人类皮肤外植体上进行评估。目的：研究HPGA滤膜对培养细胞的透皮情况。 将对人类皮肤进行调查。成功标准：这一目标将在确定 在48小时的评估期后，HPGA-过滤器不能渗透到有活力的皮肤细胞。具体目标#2.扩大 生产75公斤HPGA过滤器的化学、制造和控制工艺 大小。批量生产75公斤HPGA过滤器的化学、制造和控制(CMC)工艺 尺寸将被开发出来。成功标准：这个目标将在优化程序以达到以下目标时成功 生产批量为75公斤的材料，具有可重复性的分析特性和稳定性。商业广告 机遇：到2019年，全球紫外线滤清器市场预计将超过6.5亿美元。第二阶段SBIR 研究将包括额外的研究，以确认对更多志愿者的安全性；检查 针对领先的商用防晒霜的性能；并优化化学、制造和控制 (CMC)工艺以生产几千克数量的过滤器。这项技术由一项悬而未决的 保护博士商业利益和发展利益的专利。

PROJECT SUMMARY / ABSTRACT This Phase II project is predicated on the NCI Phase I award 1R43CA236265-01 and is a resubmission. Problem to be Solved and Significance: Exposure to Ultraviolet radiation (UVR) is a risk factor for the development of skin cancer, and health care agencies recommend that sunscreens be used as a preventative measure. A major limitation of commercial sunscreens is the need to continually reapply to gain full benefit. This is because sunscreens contain UV filters that lack affinity with skin and are easily removed by normal wear. The development of durable filters with improved retention on skin has the potential to mitigate UV- mediated toxicities and remains a significant priority. Product and Long-Term Goal: Nanometics (d.b.a. PHD Biosciences [PHD]) is developing novel titanium dioxide and zinc oxide UV filters that contain a coating that interacts with skin proteins to improve topical retention time for up to 160 min. The novel UV filters are as photoprotective and safe as commercial UV filters and readily synthesized from inexpensive starting materials. They will be sold globally as ingredients for sunscreens and other topical products. It is anticipated that these UV filters will alleviate the need for constant product reapplication. Technological Innovation: The surface of commercial titanium dioxide and zinc oxide UV filters is covalently modified to contain a coating that interacts with skin proteins to improve topical retention time. The coating is designed to form a stable interaction at skin pH and can easily be removed by washing with soap and water. Specific Aim #1 Demonstrate that modification with HPGA does not influence the dermal penetration profile of the UV filters when evaluated on human skin explants. In this aim the dermal penetration profile of HPGA-Filters on cultured human skin will be investigated. Success Criterion: This aim will be successful upon determining that the HPGA-Filters do not penetrate to viable skin cells after a 48 h evaluation period. Specific Aim #2. Scale the chemistry, manufacturing and control processes to produce the HPGA-Filters on 75 kilogram batch sizes. The chemistry, manufacturing, and control (CMC) processes to produce HPGA-Filters in 75 kg batch sizes will be developed. Success Criterion: This aim will be successful upon optimizing the procedure to produce materials at 75 kg batch sizes with reproducible analytical profile and stability. Commercial Opportunity: The global market for UV filters is estimated to exceed $650 million by 2019. Phase II SBIR studies will include additional studies to confirm the safety on a larger number of volunteers; examine the performance against leading commercial sunscreens; and optimize the chemistry, manufacturing, and control (CMC) processes to produce the filters in multi-kilogram quantities. The technology is covered by a pending patent that protects the PHD commercial and development interests.