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

单体序列的操作作为在聚合物中产生结构和功能的手段对于天然聚合物（例如DNA和蛋白质）是公认的。 然而，对于合成聚合物，精确控制其结构单元的序列是极其困难的，如果不是不可能的话。对于序列控制中的低保真度就足够的应用，特定序列控制的有用替代方案是采用统计方法，从成本效益的角度来看，这可能是优选的。拟议的研究旨在使用统计序列控制开发具有改善的生物降解和药物释放性能的药物递送应用的聚合物材料。 研究的重点是开发具有改善的生物降解性和药物释放性能的聚（D，L-乳酸-乙醇酸）（PLGA）共聚酯。 PLGA是药物递送应用中使用的最普遍的聚合物材料。目前，商业PLGA聚合物通过间歇式共聚反应生产，由于丙交酯（LA）和乙交酯（GL）单体对聚合的不同反应性，其通常生产非顺序控制的“梯度PLGA”共聚物。拟议的研究将旨在推进开环聚合的基本理解，以控制单体序列分布沿着无规共聚物PLGA，并开发一个框架，以了解单体序列分布如何影响药物的封装和释放性能的聚合物。提出了一系列结构-性质研究来探讨序列与药物递送之间的关系。工作范围是基础性的，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，并教授他们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，在外联活动中演示控制释放程序。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.