72: Synthesis of copolymers from poly(2-oxazoline)s and polyesters

Synthesis of copolymers from poly(2-oxazoline)s and polyesters

Laura Mengs, Florian T. Kaps, Lisa M. Röther, Erik Wegener, Rainer Jordan.

Block copolymers are the backbone of drug delivery in application and research ability to combine varying solubilities, enabling efficient drug transport.¹ Among these, biodegradable polyesters, such as the extensively studied poly(lactide) (PLA) and its copolymer with poly(glycolide), poly(lactide-co-glycolide) (PLGA), are widely employed.² Poly(2-oxazoline)s (POx) present a versatile platform for polymer therapeutics due to their peptide-like structure and biocompatibility. Additionally, their broad range of physical and chemical properties, facilitated by numerous available monomers and adaptable end-group designs, make them ideal candidates for advanced applications.³        

We hereby present the synthesis of POx-PLGA-copolymers via organocatalyzed solvent polymerization from well-defined POx macroinitiators. This approach achieved high monomer conversion and narrow dispersities. Adjusting structural parameters, including block length ratios, block arrangements, microstructures, and the lactide-to-glycolide monomer ratio, allows for precise control over the resulting polymer properties. Notably, block copolymers with hydrophilic components demonstrated improved solubility and adjustable glass transition temperatures above 37 °C. These findings underline the potential of these materials in creating highly customizable matrices for PLGA nanoparticle coatings.

Their structural adaptability opens exciting opportunities for example in cancer therapy.⁴

References

1.         Wang C.H., Hsiue GH. New amphiphilic poly(2-ethyl-2-oxazoline)/ poly(L-lactide) triblock copolymers. Biomacromolecules. 2003;4(6):1487-1490. doi:10.1021/bm034190s

2.         Zhang K, Tang X, Zhang J, et al. PEG-PLGA copolymers: Their structure and structure-influenced drug delivery applications. Journal of Controlled Release. 2014;183(1):77-86. doi:10.1016/j.jconrel.2014.03.026

3.         Luxenhofer R, Han Y, Schulz A, et al. Poly(2-oxazoline)s as polymer therapeutics. Macromol Rapid Commun. 2012;33(19):1613-1631. doi:10.1002/marc.201200354

4.         Matos AI, Peres C, Carreira B, et al. Polyoxazoline-Based Nanovaccine Synergizes with Tumor-Associated Macrophage Targeting and Anti-PD-1 Immunotherapy against Solid Tumors. Advanced Science. 2023;10(25):1-22. doi:10.1002/advs.202300299