Margarita Harrera-Alonso, Johns Hopkins University
October 9, 2014
Functional Polycarbonates as Environmentally Responsive
Abstract:
Organoboron polymers play important roles in biomedical applications. An ample number of monomers bearing boronic acid derivatives have been synthesized, particularly focusing on controlled free radical polymerization methods. Organoboron polymers synthesized by ringopening polymerization (ROP) routes are far less explored. We discuss our recent efforts on the synthesis of boronic acid-installed cyclic carbonates by ROP and the use of these materials as polymeric prodrugs.Environmental responsiveness is an appealing trait of emerging polymeric materials, as shown for a variety of pH responsive drug delivery systems. The chemical versatility of the conjugation site and conjugate lability to physiologically relevant changes in pH, will largely determine their applicability. We have synthesized a series of boronic acid-functionalized polycarbonates (PPBC) with high precision, and used them for the formation of a drug-polymer complex with the capability to undergo pH-sensitive delivery of a diol-containing drug, capecitabine (CAPE). Complexation of CAPE with a PEGylated- PPBC block copolymer, via boronic ester formation, resulted in amphiphiles capable of self- assembling into spherical nanoparticles. We examined nanoparticle stability and release kinetics in neutral and acidic media, and relate differences in release profiles and particle stability with changes to polymer chemistry. Comparison of complexed nanoparticles with their non-complex analogs revealed striking differences in release rate and particle stability. Illustrated herein for capecitabine, the pH-sensitive dissociation of boronate esters from PPBCs can be applied in a general manner to diol- or catechol-containing solutes, demonstrating the utility of these polymers for biomedical applications.
Date posted
Jun 17, 2019
Date updated
Jun 17, 2019