Fabrication of citric acid crosslinked β‐cyclodextrin/hydroxyethylcellulose hydrogel films for controlled delivery of poorly soluble drugs

Abstract

β‐cyclodextrin grafted hydroxyethylcellulose (βCD‐g‐HEC) hydrogel films were prepared for the controlled release of poorly soluble model drug (ketoconazole) using citric acid as crosslinking agent. The active βCD and carboxyl content of the hydrogel films were determined by phenolphthalein assay and acid–base titration. The films were characterized by solid state 13C NMR, ATR–FTIR, thermogravimetric analysis, and differential scanning calorimetric, and analyzed for tensile strength, swelling ratio, drug loading, release, hemocompatibility, in vitro cytotoxicity, and implantation test. An increase in the concentration of βCD in feed increased the active βCD content of the hydrogel films but reduced their extent of interpolymer crosslinking. The βCD‐g‐HEC hydrogel films with high active βCD content showed maximum drug loading whereas those with high crosslinking density were capable of controlling the drug release for long duration. Hemolysis assay and in vitro cytotoxicity study revealed the biocompatible nature of the hydrogel films whereas implantation test indicated their minimal inflammatory effect. From the overall results, βCD‐g‐HEC hydrogel films were found to be better alternative to the previously reported βCD‐HPMC and βCD‐CMC hydrogel films for enhanced loading and long‐term release, respectively, of the poorly soluble drugs. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46452.

Crosslinkers for polysaccharides and proteins: Synthesis conditions, mechanisms, and crosslinking efficiency, a review

“…After esterification reaction, only one peak still remains present in the solid-state spectrum, reinforcing that the two ester groups are used as crosslinking sites in hydrogels, moreover, the position of the chemical shifts changes and they become weaker. Many authors inferred this event as a consequence of esterification reactions with several natural polymers [353][354][355][356]. The presence of ester linkages and free carboxylic acid groups might broaden the peak at 174.3 ppm [357].…”