Polyplex Formation Influences Release Mechanism of Mono- and Di-Valent Ions from Phosphorylcholine Group Bearing Hydrogels

A Wilson,Mark Blenner,Anthony Guiseppi-Elie

doi:10.3390/polym6092451

Abstract

The release of monovalent potassium and divalent calcium ions from zwitterionic phosphorylcholine containing poly(2-hydroxyethyl methacrylate) (pHEMA)-based hydrogels was studied and the effects of polymer swelling, ion valence and temperature were investigated. For comparison, ions were loaded during hydrogel formulation or loaded by partitioning following construct synthesis. Using the Koshmeyer-Peppas release model, the apparent diffusion coefficient, Dapp, and diffusional exponents, n, were Dapp (pre-K+) = 2.03 × 10−5, n = 0.4 and Dapp (post-K+) = 1.86 × 10−5, n = 0.33 respectively, indicative of Fickian transport. The Dapp (pre-Ca2+) = 3.90 × 10−6, n = 0.60 and Dapp (post-Ca2+) = 2.85 × 10−6, n = 0.85, respectively, indicative of case II and anomalous transport. Results indicate that divalent cations form cation-polyelectrolyte anion polymer complexes while monovalent ions do not. Temperature dependence of potassium ion release was shown to follow an Arrhenius-type relation with negative apparent activation energy of −19 ± 15 while calcium ion release was temperature independent over the physiologically relevant range (25–45 °C) studied. The negative apparent activation energy may be due to temperature dependent polymer swelling. No effect of polymer swelling on the diffusional exponent or rate constant was found suggesting polymer relaxation occurs independent of polymer swelling.

Highlights

Hydratable cross-linked polymers, or hydrogels, have become a mainstay in biological and biomedical applications [1] due to their desirable properties engendered by controllable high degree of hydration [2,3], cell and tissue biocompatibility [4] and high potential for molecular engineering [5]
It was shown that ion charge played the most significant role in the mechanism of release
This is primarily caused by a weak interaction between divalent cations and polyelectrolyte anions forming polymer-ion complexation sites which govern release

Summary

Introduction

Hydratable cross-linked polymers, or hydrogels, have become a mainstay in biological and biomedical applications [1] due to their desirable properties engendered by controllable high degree of hydration [2,3], cell and tissue biocompatibility [4] and high potential for molecular engineering [5]relative to other materials. The effects of hydrogel swelling dynamics; solute transport properties; in situ kinetics of enzymatic and/or binding recognition reactions; ionic interactions; and environmental (pH, temperature, ionic strength) changes can alter the performance of a biologically responsive system [15,19,20,21]. These factors greatly influence polymer design and could have unforeseen consequences on the release profiles of the delivered drugs, impacting safety and/or efficacy

Methods

Results

Conclusion