Osteogenic Calcium Phosphate Nanoparticles with Designable Drug Release Kinetics

描述(由申请人提供)：这份K99/R00指导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Vuk Uskokovic博士是一名物理化学家和纳米技术专家，他希望通过这一奖项获得细胞培养实验和其他生物分析方法领域的额外培训。他的目标是发展多功能和纳米结构生物材料领域的研究技能，用于修复硬组织。这项提议的目标将增强乌斯科科维奇博士在制造智能生物材料方面的知识，该材料用于同时进行时间控制的药物释放和患病硬组织的再生。提出了一种包覆克林霉素的磷酸钙/聚合物复合微粒的合成方法，并对该材料的体外抗菌性能和骨诱导性能进行了测试。这项拟议研究的中心假设是，化学计量比和磷酸钙的颗粒大小可以用来调整包囊药物的释放动力学。Uskokovic博士将在包括Tejal Desai博士、Grayson Matt博士、Stefan Habelitz博士、吴丽博士和Peter Lomer博士在内的专家指导团队的指导下进行培训和研究活动。他将接受毛罗·法拉利、安东尼·托姆西亚和查尔斯·胡佛博士的额外咨询。鉴于口腔和颅面组织再生的生物工程和生物材料研究方法已被NIDCR选为优先目标之一(目标I-5，目标1，NIDCR战略计划2009-2013年)，本申请的目标将解决非常实际的口腔、牙齿和颅面健康问题。除了Uskokovic博士在材料科学和工程方面的专业知识和加州大学旧金山分校牙科学校的支持外，通过这个独立之路奖培训Uskokovic博士也符合NIDCR战略计划目标2的所有三个目标。UCSF牙科学校是过去15年来NIH资助最多的牙科学校。Uskokovic博士将进行一项研究，该研究将涉及：a)通过超声搅拌乳剂的共沉淀法合成多功能治疗性和骨诱导性磷酸钙纳米颗粒；b)细菌和细胞培养中的药物释放研究。对于提出的假设，本研究的中心目的是推导出磷酸钙载体的溶出度和药物释放效率与其化学组成和微观结构之间的基本关系。这项K99/R00奖旨在获得R01奖金，奖金的撰写工作将在奖励期结束前开始。

DESCRIPTION (provided by applicant): 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.