Synthesis and Evaluation of a Thermoresponsive Degradable Chitosan-Grafted PNIPAAm Hydrogel as a "Smart" Gene Delivery System.

Monika Ziminska,Emma Mcerlean,Helen O Mccarthy,Nicholas Dunne,Jordan J Wilson

doi:10.3390/ma13112530

Abstract

Thermoresponsive hydrogels demonstrate tremendous potential as sustained drug delivery systems. However, progress has been limited as formulation of a stable biodegradable thermosensitive hydrogel remains a significant challenge. In this study, free radical polymerization was exploited to formulate a biodegradable thermosensitive hydrogel characterized by sustained drug release. Highly deacetylated chitosan and N-isopropylacrylamide with distinctive physical properties were employed to achieve a stable, hydrogel network at body temperature. The percentage of chitosan was altered within the copolymer formulations and the subsequent physical properties were characterized using 1H-NMR, FTIR, and TGA. Viscoelastic, swelling, and degradation properties were also interrogated. The thermoresponsive hydrogels were loaded with RALA/pEGFP-N1 nanoparticles and release was examined. There was sustained release of nanoparticles over three weeks and, more importantly, the nucleic acid cargo remained functional and this was confirmed by successful transfection of the NCTC-929 fibroblast cell line. This tailored thermoresponsive hydrogel offers an option for sustained delivery of macromolecules over a prolonged considerable period.

Highlights

Hydrogels are three-dimensional, crosslinked polymeric networks capable of absorbing large amounts of water or biological fluids [1]
A stable thermosensitive Cs-g-PNIPAAm hydrogel system was successfully synthesized via free radical polymerization
A novel approach of altering the percentage of chitosan in the copolymer was employed to explore its role on properties of the hydrogel

Summary

Introduction

Hydrogels are three-dimensional, crosslinked polymeric networks capable of absorbing large amounts of water or biological fluids [1] This group of synthetic biomaterials encompasses a wide range of chemical compositions and bulk physical properties, since they can be prepared from a vast library of available monomers and crosslinkers [2]. The therapeutic cargo dissolved within the structure of hydrogel is shielded from injection-associated shear forces and can be released with complex dynamics in a controlled manner [12]. These injectable hydrogels can be prepared using non-toxic chemical crosslinkers, enzymes, or physical interactions, such as hydrophobic and ionic interactions, and can respond to external stimuli (e.g., temperature, pH, and light), conferring “smart” or “intelligent”

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