Rapid generation of well‐defined biodegradable poly(lactide‐co‐glycolide) libraries through chromatographic separation

Abstract

AbstractPoly(lactide‐co‐glycolide) (PLGA) is a biodegradable copolymer and widely used in pharmaceuticals. Commercially available PLGAs are produced through ring‐opening polymerization, which results in inevitable dispersity in molecular weight and chemical composition (i.e., lactide‐to‐glycolide ratio), influencing bulk properties such as degradation, mechanics, and morphology. In this study, an automated chromatographic separation technique was employed to generate a series of well‐defined, low‐dispersity fractionated PLGAs from a single commercially available PLGA (lactide‐to‐glycolide ratio = 50:50). The structural and compositional dependence of properties for pharmaceutical applications in the form of nanofibers and nanoparticles were systematically investigated. The properties of new PLGAs by further separation were significantly dependent on composition. The molecular weight ranges were reduced, while the morphology of nanofibers and nanoparticles became more uniform. Importantly, the stability, mechanical strength, and drug loading increased, and the period of sustained release profile also increased. In brief, our data show that the automated chromatographic separation technique allows for precise control of the molecular weight and lactide‐to‐glycolide composition ratio of PLGA, in contrast to the traditional method. The use of well‐defined and fractionated new PLGA materials holds significant promise for enhancing the potential of PLGA in future pharmaceutical applications.