D--tocopherol polyethylene glycol succinate and Poloxamer 188 modified liposomal chrysin hydrogel for enhanced topical treatment of ultraviolet-induced skin photoaging damage

Chrysin (CHR) has a wide range of pharmacological and physiological activities and low toxicity, however, its clinical application is hampered by its insolubility in water, low intestinal absorption and reduced activity due to rapid carbonylation and metabolism of the hydroxyl groups at positions 5 and 7. Here, we describe a new preparation of CHR-loaded liposomal gel (CHR-LipGel) with good physicochemical stability and efficient antiphotoaging properties. The CHR-loaded liposomes (CHR-Lip) was hybridized with D-a-tocopherol polyethylene glycol succinate and Poloxamer 188, and dispersed in sodium hyaluronate-formed hydrogel to obtain CHR-Lip-Gel. The resulting CHR-Lip in the hydrogel had a complete vesicle structure, with a particle size of 143.50 +/- 8.20 nm. CHR-Lip-Gel significantly (p < 0.01) increased skin permeability and skin retention of chrysin compared with CHR aqueous dispersion (CHR group). Cellular uptake in human immortalized keratinocytes (HaCaT) revealed the superiority of the liposomal formulations over the free drug (p < 0.01). CHR-Lip-Gel markedly (p < 0.01) reduced the reactive oxygen species content and showed a dose dependency after UV irradiation on HaCaT cells in vitro. Additionally, both CHR-Lip-Gel and CHR-Lip groups decreased malondialdehyde and increased the contents of superoxide dismutase, hydroxyproline and glutathione peroxidase significantly (p < 0.05) in the UV-treated HaCaT cells in vitro compared with CHR group. Anti-photoaging studies in UVinjured rats showed that CHR-Lip-Gel observably increased the preventive and therapeutic effects compared with CHR-Lip, CHR, or epigallocatechin gallate. All the administration groups inhibited the expression of matrix metalloprotein-1 and promoted the expression of transforming growth factor-b1; however, only CHR-Lip-Gel and epigallocatechin gallate showed statistically significant differences ( p < 0.01) in regulating both of these proteins in contrast with the model control group. This newly developed carrier effectively increased the skin permeation of chrysin, thereby significantly enhancing its efficacy. In summary, our study suggests that CHR-Lip-Gel is a superior anti-photoaging system. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).