Synthesis and in vitro assessment of anticancer hydrogels composed by carboxymethylcellulose-doxorubicin as potential transdermal delivery systems for treatment of skin cancer

Malignant melanoma is the most lethal form of skin cancer in humans which is difficult to treat by conventional surgery and chemotherapeutics. Despite unquestionable progresses in recent years demonstrated by anticancer drug carriers to target tumor local microenvironment, it is growing at a rate of one million new cases being reported annually because overcoming the skin physiological barriers and the side effects associated with chemotherapy still remain threatening challenges. Herein, we designed and developed a novel polysaccharide-based prodrug composed of carboxymethylcellulose (CMC) polymer with anticancer drug doxorubicin (DOX) forming electrostatic nanocomplexes in aqueous solution. The results evidenced the effect of degree of substitution (DS = 0.77 and 1.22) of CMC on the physicochemical properties of the CMC-DOX complexes associated with the formation of supramolecular colloidal nanostructures. They were stabilized by electrostatic interactions between anionic carboxylate groups from CMC and cationic amino groups of DOX while the polysaccharide polymer chain encapsulated the hydrophobic drug in the aqueous medium. Moreover, these polymer-drug nanoparticulate systems were crosslinked with citric acid for producing advanced tuned drug delivery hydrogels. The results demonstrated the effect of DS of CMC and the addition of DOX on the physicochemical properties of the hydrogel network structures produced including the swelling behavior and gel fraction. Moreover, the distinct DS of CMC tailored the DOX release kinetics in vitro showing activity for killing melanoma cancer cells while less cytotoxicity towards normal cells. To this end, an innovative platform was developed based on colloidal polysaccharide-drug nanocomplexes producing anticancer hydrogels offering promising perspectives for skin cancer applications using transdermal drug delivery chemotherapy. (C) 2018 Elsevier B.V. All rights reserved.