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

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Abstract

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.

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Acknowledgements

This work was supported by the Technological Innovation R&D Program (S2406238) funded by the Small and Medium Business Administration (SMBA, Korea) and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2018R1A6A1A03025582).

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Authors and Affiliations

  1. Department of Medical Biomaterials Engineering, College of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon, 200-701, Korea

    Tae Hoon Kim & Jin-Chul Kim

  2. R&D Center, ACT Co., Ltd., Suwon, 16506, Korea

    Dae Sung Yoo

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  1. Tae Hoon Kim
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  2. Dae Sung Yoo
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  3. Jin-Chul Kim
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Correspondence to Jin-Chul Kim.

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Kim, T.H., Yoo, D.S. & Kim, JC. In vitro Dermal Delivery of Epidermal Growth Factor Using Redox-responsive Cubosomes. Biotechnol Bioproc E 24, 273–281 (2019). https://doi.org/10.1007/s12257-018-0383-5

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  • DOI: https://doi.org/10.1007/s12257-018-0383-5

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