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In vitro Dermal Delivery of Epidermal Growth Factor Using Redox-responsive Cubosomes

Kim, Tae Hoon, Yoo, Dae Sung, Kim, Jin-Chul
Biotechnology and bioprocess engineering 2019 v.24 no.2 pp. 273-281
additives, alginates, artificial skin, cell proliferation, cytotoxicity, disulfide bonds, dithiothreitol, epidermal growth factor, permeability, reducing agents, storage temperature, thiazolyl blue
Reduction-responsive monoolein (MO) cubosome was prepared for the dermal delivery of epidermal growth factor (EGF) by including cystamine-crosslinked alginate in the water channel of the cubosome. On atomic force micrograph, the cubosome was found as round particles and it was tens of nanometers in diameter. Additives such as alginate, cystamine, and EGF seemed to have little effect on the size and the shape of cubosome. The release of EGF from the cubosome was promoted by dithiothreitol (DTT, a reducing agent), possibly because the disulfide bond of the cross-linker (cystamine) might be broken by the reducing agent. The cubosome promoted the permeation of EGF through an artificial skin mounted on a diffusion cell. Thiazolyl blue tetrazolium bromide (MTT) assay revealed that the cubosome exhibited no marked cellular toxicity after it was incubated with cell (CCD-986sk) for 24 h as long as the concentration was not greater than 20 ug/mL. Free EGF could hardly promote the cell proliferation at all the concentrations tested (0.25 ppm–1 ppm). EGF contained in the cubosome suspension significantly enhanced cell proliferation when EGF concentration was 0.75 and 1 ppm. EGF contained in the cubosome suspension could maintain about 85% of the initial biological activity while it was stored at 25°C for 4 weeks.