Phenylboronic Acid-Installed Polycarbonates for the pH-Dependent Release of Diol-Containing Molecules

Abstract

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. Herein, we report on the use of a drug–polymer complex based on boronic acid-functionalized polycarbonates (PPBC) as the substrate for the 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 noncomplex analogues 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.

Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release

“…383–390 A considerable advantage offered by polycarbonates over polyesters is the wide range of pendant groups that can be accessed by using an appropriately functionalized monomer or by postpolymerization functionalization. 378,391 Thermoresponsive polycarbonates via the pendant group approach have been produced.…”

Phenylboronic acid-decorated polymeric nanomaterials for advanced bio-application

“…In recent years, polymeric nanoparticles with different architectures and formulations as drug delivery carriers based on PBA-SA recognition for cancer therapeutics were investigated by many researchers [55][56][57]64]. Deshayes et al prepared PBA-installed polymeric micelles to target sialylated epitopes overexpressed on cancer cells, and the micelles showed high affinity for SA even under intratumoral pH conditions, suggesting the potential [64].…”

Iminoboronate-based dual-responsive micelles via subcomponent self-assembly for hydrophilic 1,2-diol-containing drug delivery

“…As far as neutral hydrophilic drugs are concerned, a feasible way to incorporate them in polymeric micelles is conjugating to polymers via stimuli-responsive covalent bonds considering the nanocarrier stability during circulation and fast drug-release at target tissue. 12,[15][16][17] Recently, Herrera-Alonso et al prepared a hydrophilic drug conjugated polymer complex based on boronic esterication between a diol-containing anticancer drug, capecitabine (CAPE), and phenylboronic acid-functionalized polycarbonates under anhydrous conditions.…”