Osteogenic Calcium Phosphate Nanoparticles with Designable Drug Release Kinetics

具有可设计药物释放动力学的成骨磷酸钙纳米颗粒

• 批准号: 8301509
• 负责人: Vuk Uskokovic
• 金额: $ 8.83万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8301509
• 关键词: Address; Antibiotics; Antifungal Agents; Area; Award; Biocompatible Materials; Biodegradation; Biological; Biomaterials Research; Biomedical Engineering; Cell Culture Techniques; Chemicals; Clindamycin; Complement; Consult; Defect; Dental; Dental Schools; Drug Compounding; Drug Controls; Drug Delivery Systems; Drug usage; Emulsions; Encapsulated; Engineering; Fibroblasts; Filler; Fluorescent Dyes; Funding; Goals; Grant; Growth Factor; Health; Hemostatic Agents; Image; In Vitro; Institutes; Intravenous; K-Series Research Career Programs; Kinetics; Knowledge; Lead; Marshal; Mentors; Methods; Morphology; Natural regeneration; Oral; Osteoblasts; Osteomyelitis; Particle Size; Pathway interactions; Performance; Pharmaceutical Preparations; Phase; Polymers; Precipitation; Procedures; Property; Protocols documentation; Research; Research Activity; Research Training; Science; Solutions; Strategic Planning; Suspension substance; Suspensions; Testing; Therapeutic; Time; Tissues; Training; Training Activity; Training Programs; Trauma; United States National Institutes of Health; Work; Writing; antimicrobial; base; bone; calcium phosphate; craniofacial; design; drug production; implantation; nanoparticle; nanosized; nanostructured; osteogenic; particle; response; skills; stoichiometry; theranostics

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.

描述（由申请人提供）：此 K99/R00 指导研究职业发展奖申请正在提交给国家牙科和颅面研究所 (NIDCR)。候选人 Vuk Uskokovic 博士是一位物理化学家和纳米技术专家，他寻求通过该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。他的目标是发展用于修复硬组织的多功能和纳米结构生物材料领域的研究技能。该提案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，以实现同步时间控制的药物释放和患病硬组织的再生。提议合成封装克林霉素（一种用于治疗骨髓炎的药物）的磷酸钙/聚合物复合颗粒，并测试给定材料的体外抗菌特性和诱导性能。该研究的中心假设是磷酸钙的化学计量和粒径可用于调节封装药物的释放动力学。乌斯科科维奇博士将在包括博士在内的专家指导团队的指导下进行培训和研究活动。特加尔·德赛、格雷森·马歇尔、斯特凡·哈贝利茨、吴力和彼得·卢默。他将接受博士的额外咨询。毛罗·法拉利、安东尼·托姆西亚和查尔斯·胡佛。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 选择为优先目标之一（目标 I-5，目标 1，NIDCR 战略计划 2009-2013），当前申请的目标将解决高度实际的口腔、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以及 UCSF 牙科学院（过去 15 年来 NIH 资助最多的学院）的支持之外，通过独立之路奖对 Uskokovic 博士进行培训也符合 NIDCR 战略计划目标 2 的所有三个目标。 Uskokovic 博士将进行一项研究，其中涉及： a) 通过超声波搅拌乳液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) 细菌和细胞培养物中的药物释放研究。关于所提出的假设，本研究的中心目的是得出磷酸钙基载体的溶出率和药物递送效率及其化学成分和微观结构之间的基本相关性。该 K99/R00 奖项旨在获得 R01 补助金，该补助金的撰写将在奖励期结束之前开始。

项目成果

Major Challenges for the Modern Chemistry in Particular and Science in General.

现代化学（特别是现代化学）和一般科学的主要挑战。

• DOI: 10.1007/s10699-010-9185-8
• 发表时间: 2010
• 期刊: Foundations of science
• 影响因子: 0.9
• 作者: Uskokovíc,Vuk

Entering the era of nanoscience: time to be so small.

• DOI: 10.1166/jbn.2013.1642
• 发表时间: 2013-09
• 期刊: Journal of biomedical nanotechnology
• 影响因子: 2.9
• 作者: Uskoković V

A new, simple, green, and one-pot four-component synthesis of bare and poly(α,γ, L-glutamic acid)-capped silver nanoparticles.

• DOI: 10.1007/s00396-011-2540-7
• 发表时间: 2012-02-01
• 期刊: Colloid and polymer science
• 影响因子: 2.4
• 作者: Stevanović M;Savanović I;Uskoković V;Skapin SD;Bračko I;Jovanović U;Uskoković D
• 通讯作者: Uskoković D

Dynamic Light Scattering Based Microelectrophoresis: Main Prospects and Limitations.

• DOI: 10.1080/01932691.2011.625523
• 发表时间: 2012-12-01
• 期刊: Journal of dispersion science and technology
• 影响因子: 2.2
• 作者: Uskoković V

When Nothing Turns Itself Inside out and Becomes Something: Coating Poly(Lactic-Co-Glycolic Acid) Spheres with Hydroxyapatite Nanoparticles vs. the Other Way Around.

• DOI: 10.3390/jfb13030102
• 发表时间: 2022-07-23
• 期刊: Journal of functional biomaterials
• 影响因子: 4.8