Abstract
PL(G)A-PEG block polymers have been widely used in a variety of drug delivery applications but are inherently limited in terms of their capacity for functionalization and thus customization to specific delivery tasks. Herein, we report synthetically tunable and functionalizable brush co-polymer analogues of conventional PL(G)A-PEG polymers fabricated via atom transfer radical polymerization (ATRP) of methacrylate-based co-monomers with oligo(lactic acid) side chains in the hydrophobic block and oligo(ethylene glycol) side chains in the hydrophilic block. Block co-polymers prepared by varying the molecular weights of each block, the functionality of either block (via functional monomer copolymerization), as well as the number of lactic acid repeat units in the hydrophobic block were subsequently used to fabricate nanoparticles with sizes of 100–500 nm and tunable degradation rates via flash nanoprecipitation. The resulting nanoparticles exhibited high colloidal stability (consistent with the dense brush-like POEGMA interface), favorable in vitro cytocompatibility, and the capacity for effective drug loading (>96% encapsulation efficiency for paclitaxel and 41% even for the hydrophilic therapeutic doxorubicin hydrochloride). Furthermore, functionalization of the hydrophobic POLAMA block with methacrylic acid residues enabled controlled dissolution of the nanoparticle over time, offering potential to tune drug release via an alternative mechanism not readily accessible with conventional PLA-PEG-based block copolymers. Combining these properties with the flexible chemical compositions and the generally recognized as safe degradation properties of the brush polymer analogues, POLAMA-b-POEGMA polymers represent a highly versatile platform for nanoparticle-based drug delivery applications.
Published Version
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