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

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.

Physicochemical Investigations of Chitosan-Based Hydrogels Containing Aloe Vera Designed for Biomedical Use

“…This polysaccharide has been used by Venkatesan et al for the synthesis of hydrogels containing, additionally, carbon nanotubes and such materials have been analyzed in view of their antimicrobial activity [ 22 ]. Another solution was presented by Ziminska et al They prepared hydrogel polymers based on chitosan-grafted poly( N -isopropylacrylamide) and proved that such materials may be used for sustained delivery of genes [ 23 ]. Other frequently used natural polymers in the preparation of hydrogel materials are starch [ 24 ], gelatin [ 25 ], hyaluronic acid [ 26 ], and alginates [ 27 , 28 ].…”

Poly(N-isopropylacrylamide)-Based Hydrogels for Biomedical Applications: A Review of the State-of-the-Art

“…Correspondingly, HOOC-PNIPAM - b -poly(2-(dimethylamino) acrylate)-C 12 H 25 /DNA (HOOC-PNIPAM- b -QPDMAEA-C 12 H 25 /DNA) [ 191 ], chitosan- g -PNIPAM) (CPN)@graphene oxide (GO)-cetuximab (CET)/irinotecan (CPT-11)@short hairpin RNA (shRNA) hydrogel (CPN@GO-CET/CPT11@shRNA) [ 216 ] and siRNA@poly(2-dimethylaminoethyl methacrylate) (PDMAEMA)/PNIPAM-PEG-PNIPAM hydrogel (siRNA@PDMAEMA/PNIPAM-PEG-PNIPAM) [ 217 ] systems were formulated by researchers and demonstrated promising results in gene delivery. Table 2 demonstrates the latest studies on PNIPAM-based hydrogels in gene delivery.…”

Injectable Natural Polymer Hydrogels for Treatment of Knee Osteoarthritis

“…For example, the temperature‐sensitive polymer, poly( N ‐isopropylacrylamide) (PNIPAAm) has been grafted onto chitosan backbone through the amine groups as an injectable “smart” gene delivery system using conventional free radical polymerization. [ 78 ] Other polysaccharides (e.g., cellulose, xyloglucan, and agarose) have also been explored for making thermally reversible hydrogels. [ 79 ] A thermal reversible pluronic‐alginate‐hyaluronic acid hydrogel was developed to provide the sustained release of glucosamine for OA treatment.…”