Osteogenic Calcium Phosphate Nanoparticles with Designable Drug Release Kinetics

这份K99/R00导师研究职业发展奖的申请正在提交给 国家牙科和颅面研究所(NIDCR)。候选人，武克博士 Uskokovic是一名物理化学家和纳米技术学家，他寻求在 细胞培养实验和其他生物分析方法的领域 获奖。他的目标是发展多功能和纳米结构领域的研究技能 用于修复硬组织的生物材料。这项提案的目标将增强Dr。 Uskokovic在制造同时时间控制的智能生物材料方面的知识 药物释放和病变硬组织的再生。提出了钙的合成 磷酸盐/聚合物复合微粒包裹克林霉素，一种用于治疗的药物 骨髓炎的治疗，以及抗菌性能和骨诱导作用的检测 给定材料在体外的性能。拟议研究的中心假设是 磷酸钙的化学计量比和颗粒大小可以用来调整动力学 释放封装的药物。乌斯科维奇博士将进行他的培训和研究活动 在包括Tejal Desai博士在内的专家指导团队的指导下，Grayson 马歇尔、斯特凡·哈伯利茨、吴莉和彼得·鲁默。他将接受来自以下机构的额外咨询 毛罗·法拉利博士、安东尼·托姆西亚博士和查尔斯·胡佛博士。考虑到生物工程和 口腔和颅面组织再生的生物材料研究方法 被NIDCR选为优先目标之一(目标I-5，目标1，NIDCR战略 计划2009-2013)，本申请的目标将针对高度实际的口腔、牙科和 头面部健康问题。通过这条通往独立的道路培训乌斯科科维奇博士 除了他在材料科学和工程方面的专长以及加州大学旧金山分校的支持外，他还获得了奖项 牙科学校是美国国立卫生研究院在过去15年里资助最多的一所学校，也符合所有这三项要求 NIDCR战略计划目标2的目标。乌斯科维奇博士将进行一项研究， 涉及：a)多功能治疗性和诱导性磷酸钙的合成 超声搅拌乳剂共沉淀法制备纳米粒子；b)药物 发表细菌和细胞培养方面的研究。关于拟议的假设， 这项研究的中心目的是得出溶出度和溶出度之间的基本关系。 磷酸钙基载体的药物传递效率及其化学组成和 微观结构。本K99/R00奖旨在获得R01奖金，其撰写 将在授权期结束前开始。

This K99/R00 Mentored Research Career Development Award application is being submitted to the National Institute on Dental and Craniofacial Research (NIDCR). The candidate, Dr. Vuk Uskokovic, is a physical chemist and nanotechnologist who seeks to obtain additional training in the area of cell culture experimentation and other biological methods of analysis through this award. His aim is to develop research skills in the area of multifunctional and nanostructured biomaterials for reparation of hard tissues. The goals of this proposal would enhance Dr. Uskokovic's knowledge of fabrication of smart biomaterials for simultaneous time-controlled drug release and regeneration of diseased hard tissues. Proposed is the synthesis of calcium phosphate/polymer composite particles that encapsulate clinmadycin, a drug used in the treatment of osteomyelitis, as well as testing of the antimicrobial properties and osteinductive performance of the given material in vitro. The central hypothesis of the proposed study is that stoichiometry and the particle size of calcium phosphates can be used to tune the kinetics of the release of the encapsulated drug. Dr. Uskokovic will conduct his training and research activities under the guidance of an expert mentoring team that includes Drs. Tejal Desai, Grayson Marshall, Stefan Habelitz, Wu Li, and Peter Loomer. He will receive additional consulting from Drs. Mauro Ferrari, Antoni Tomsia, and Charles Hoover. Given that bioengineering and biomaterials research approaches to regeneration of oral and craniofacial tissues has been selected as one of the prioritized goals by the NIDCR (Objective I-5, Goal 1, NIDCR Strategic Plan 2009-2013), the goals of the current application will address highly actual oral, dental and craniofacial health problems. Training Dr. Uskokovic through this Pathway to Independence Award on top of his expertise in materials science and engineering and support by the UCSF Dental School, the most funded one by the NIH in the past 15 years, also complies with all three objectives of Goal 2 of the NIDCR Strategic Plan. Dr. Uskokovic will conduct a study which will involve: a) Synthesis of multifunctional therapeutic and osteoinductive calcium phosphate nanoparticles by means of co-precipitation from ultrasonically agitated emulsions; b) Drug release studies in bacterial and cell cultures. With respect to the proposed hypothesis, the central aim of this study is to derive fundamental correlations between the dissolution rate and drug delivery efficiency of calcium phosphate based carriers and their chemical composition and microstructure. This K99/R00 award is conceived to lead to an R01 grant, the writing of which will begin before the end of the award period.