Curcumin-loaded layer-by-layer folic acid and casein coated carboxymethyl cellulose/casein nanogels for treatment of skin cancer

Targeted drug delivery systems using natural polysaccharide/protein biopolymer for tumor cells are an attractive platform for enriching the therapeutic effects and reducing the side effects of the drug. Carboxymethyl cellulose (CMC) and casein (CA) nanogels (NGs) loaded with curcumin (CUR) were prepared by self-assembly method and fabricated with folic acid (FA) and casein using layer-by-layer (LbL) technique for skin cancer drug delivery. The prepared samples were characterized by techniques like zeta potential, FTIR, XRD, TGA and Cryo-SEM. Both the swelling and in vitro drug release was performed in acidic pH (4.5 and 6.8) and physiological pH 7.4. Hemolysis assays demonstrated that the drug carriers are hemocompatible. Confocal microscope studies indicate facilitated uptake of 2-FA/CA/CUR@CMC-CA NGs in MEL-39 melanoma cancer cell line, which in turn result in a higher potential for apoptosis. Compared to pure CUR and CUR@CMC-CA NGs, the 2-FA/CA/CUR@CMC-CA NGs has lower IC50 value and superior cytotoxicity in MEL-39 cells because of folate-receptor mediated endocytosis evaluated by the cellular viability quantification using MTT assay and optical microscope images. Finally from in vitro skin permeation experiments, 2-FA/CA/CUR@CMC-CA NGs showed 3.47±0.03 to 4.15±0.25μg/ml CUR concentrations at the stratum corneum, epidermal and dermal layers. Overall, our results put forth 2-FA/CA/CUR@CMC-CA NGs as an aspiring candidate to achieve enhanced anticancer effects against melanoma skin cancer.