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

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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.