Abstract
Nanocomposite hydrogels have found a wide scope in regenerative medicine, tissue engineering, and smart drug delivery applications. The present study reports the formulations of biocompatible nanocomposite hydrogel films using carboxymethyl cellulose-hydroxyethyl cellulose-acrylonitrile-linseed oil polyol (CHAP) plain hydrogel and Na-montmorillonite (NaMMT) dispersed CHAP nanocomposite hydrogel films (NaCHAP) using solution blending technique. The structural, morphological, and mechanical properties of resultant nanocomposite hydrogel films were further investigated to analyze the effects of polyol and NaMMT on the characteristic properties. The synergistic effect of polyol and nanofillers on the mechanical strength and sustained drug-release behavior of the resultant hydrogel films was studied, which revealed that the increased cross-link density of hydrogels enhanced the elastic modulus (up to 99%) and improved the drug retention time (up to 72 h at both pHs 7.4 and 4.0). The release rate of cisplatin in nanocomposite hydrogel films was found to be higher in CHAP-1 (83 and 69%) and CHAP-3 (79 and 64%) than NaCHAP-3 (77 and 57%) and NaCHAP-4 (73 and 54%) at both pHs 4.0 and 7.4, respectively. These data confirmed that the release rate of cisplatin in nanocomposite hydrogel films was pH-responsive and increased with decrease of pH. All nanocomposite hydrogel films have exhibited excellent pH sensitivity under buffer solution of various pHs (1.0, 4.0, 7.4, and 9.0). The in vitro biocompatibility and cytotoxicity tests of these films were also conducted using 3-(4,5-dimethylthiazole-2-yl-2,5-diphenyl tetrazolium bromide) assay of human embryonic kidney (HEK-293) and human breast cancer (MCF-7) cell lines up to 48 h, which shows their biocompatible nature. However, cisplatin-loaded nanocomposite hydrogel films effectively inhibited the growth of human breast MCF-7 cancer cells. These studies suggested that the proposed nanocomposite hydrogel films have shown promising application in therapeutics, especially for anticancer-targeted drug delivery.