Statistically Sequence-Controlled Pharmaceutical Polymers, and Studies of Their Molecular Thermodynamic and Kinetic Properties

统计序列控制的药用聚合物及其分子热力学和动力学性质的研究

• 批准号: 1803968
• 负责人: You-Yeon Won
• 金额: $ 38.45万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1803968&HistoricalAwards=false
• 关键词: Statistically; Sequence; Controlled; Pharmaceutical; Polymers

The manipulation of monomer sequence as a means to produce structure and function in a polymer is well established for natural polymers, such as DNA and proteins. However, for synthetic polymers it is prohibitively difficult, if not impossible, to precisely control the sequences of their building blocks. For applications in which low fidelity in sequence control is sufficient, a useful alternative to specific sequence control is to take a statistical approach, which may be preferable from a cost-benefit standpoint. The proposed research aims to use statistical sequence control to develop polymeric materials for drug delivery applications with improved biodegradation and drug release properties. The focus of the proposed research is to develop poly(D,L-lacticco- glycolic acid) (PLGA) copolyesters having improved biodegradation and drug release properties. PLGA is the most prevalent polymeric material used in drug delivery applications. Currently, commercial PLGA polymers are produced by batch-type copolymerization reactions, which typically produce non-sequence-controlled "Gradient PLGA" copolymers because of the disparate reactivities of lactide (LA) and glycolide (GL) monomers toward polymerization. The proposed research will aim at advancing the fundamental understanding of ring-opening polymerization to control monomer sequence distribution along random copolymer PLGA, and developing a framework to understand how monomer sequence distribution affects drug encapsulation and release properties of the polymer. A set of structure-property studies is proposed to investigate the relationship between sequences and drug delivery. The scope of work is fundamental, and if successful, could have impact in both pharmaceutical and polymer research. The research project will provide integrated training for graduate and undergraduate students in a multidisciplinary environment and teach them skills that are necessary for developing the future generation of chemical engineering and polymer science researchers. Hands-on modules will be developed to demonstrate controlled release processes in outreach events. A Summer High School Research Experience Program is proposed and curriculum development is planned in the field of polymer, colloid and interface science.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

单体序列的操纵作为在聚合物中产生结构和功能的一种手段，对于天然聚合物，如DNA和蛋白质，是很好的确定的。然而，对于合成聚合物来说，精确控制其构建块的序列即使不是不可能，也是极其困难的。对于序列控制中的低保真度就足够的应用，特定序列控制的一个有用的替代方案是采用统计方法，从成本效益的角度来看，这可能是更可取的。这项拟议的研究旨在利用统计序列控制来开发具有更好的生物降解性和药物释放性能的药物输送应用的聚合物材料。本研究的重点是开发具有更好的生物降解性和药物释放性能的聚(D，L-乳酸-乙醇酸)共聚酯。PLGA是药物输送应用中使用最广泛的聚合物材料。目前，商品化的PLGA聚合物是通过间歇式共聚反应生产的，由于丙交酯(LA)和乙交酯(GL)单体对聚合的反应活性不同，这种共聚反应通常产生非顺序控制的“梯度PLGA”共聚物。这项研究旨在促进人们对开环聚合的基本认识，以控制无规共聚物PLGA上的单体序列分布，并开发一个框架来了解单体序列分布如何影响聚合物的药物包封性和释放性。提出了一系列结构-性质研究来研究序列和药物传递之间的关系。这项工作的范围是基础性的，如果成功，可能会对制药和聚合物研究产生影响。该研究项目将在多学科环境中为研究生和本科生提供综合培训，并向他们传授培养下一代化学工程和聚合物科学研究人员所需的技能。将开发实际操作单元，以演示外联活动中的受控释放程序。一项暑期高中研究体验计划被提出，并计划在聚合物、胶体和界面科学领域进行课程开发。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Effect of Paclitaxel Stereochemistry on X-ray-Triggered Release of Paclitaxel from CaWO4/Paclitaxel-Coloaded PEG-PLA Nanoparticles.

• DOI: 10.1021/acs.molpharmaceut.2c00148
• 发表时间: 2022-07
• 期刊: Molecular pharmaceutics
• 影响因子: 4.9
• 作者: Kaustabh Sarkar;Sandra E Torregrossa-Allen;B. Elzey;Sanjeev K. Narayanan;M. Langer;G. Durm;You-Yeon Won-Yo

Enhancement of Mechano-Sensitivity for Spiropyran-Linked Poly(dimethylsiloxane) via Solvent Swelling

• DOI: 10.1021/acs.macromol.0c00985
• 发表时间: 2020-09-22
• 期刊: MACROMOLECULES
• 影响因子: 5.5
• 作者: Kim, Dong Woo;Medvedev, Grigori A.;Kim, Jaewoo
• 通讯作者: Kim, Jaewoo

Strategy for Synthesis of Statistically Sequence-Controlled Uniform PLGA and Effects of Sequence Distribution on Interaction and Drug Release Properties

统计序列控制的均匀 PLGA 的合成策略以及序列分布对相互作用和药物释放特性的影响

• DOI: 10.1021/acsmacrolett.1c00637
• 发表时间: 2021
• 期刊: ACS Macro Letters
• 影响因子: 7.015
• 作者: Yoo, Jin;Viswanath, Dhushyanth;Won, You-Yeon
• 通讯作者: Won, You-Yeon

Investigation of the Mechanisms and Kinetics of DBU-Catalyzed PLGA Copolymerization via a Full-Scale Population Balance Analysis

• DOI: 10.1021/acs.iecr.1c03096
• 发表时间: 2021-10
• 期刊: Industrial & Engineering Chemistry Research
• 影响因子: 4.2
• 作者: Samruddhi Patil;Jin-Bok Yoo;You-Yeon Won

Pilot-Scale Optimization of the Solvent Exchange Production and Lyophilization Processing of PEG–PLA Block Copolymer-Encapsulated CaWO 4 Radioluminescent Nanoparticles for Theranostic Applications

用于治疗诊断应用的 PEG-PLA 嵌段共聚物封装的 CaWO 4 放射发光纳米颗粒的溶剂交换生产和冻干工艺的中试规模优化

• DOI: 10.1021/acs.iecr.0c05852
• 发表时间: 2021
• 期刊: Industrial & Engineering Chemistry Research
• 影响因子: 4.2
• 作者: Patel, Anish P.;Schorr, Christopher R.;Viswanath, Dhushyanth;Sarkar, Kaustabh;Streb, Natalie J.;Pizzuti, Vincenzo J.;Misra, Rahul;Lee, Jaewon;Won, You-Yeon
• 通讯作者: Won, You-Yeon