Enhanced Anti-Photoaging Effects of Adipose-Derived Stem Cell (ADSC) Secretome via Liposomal and Iontophoretic Intradermal Delivery

The growing societal concern regarding skin aging caused by ultraviolet (UV) exposure has spurred the quest for effective therapeutic solutions. Among these, secreted factors derived from adipose-derived stem cells (ADSC) have emerged as promising candidates with anti-photoaging properties. The secretome of ADSC stimulates resident fibroblasts, triggering antioxidant effects and promoting the synthesis of the extracellular matrix, thus counteracting the effects of photoaging. In this study, the potential of dried ADSC secretome (AD-Sc), obtained through a compressed fluid antisolvent process, is assessed as an anti-photoaging agent. In addition, liposome nanocarriers are used to encapsulate AD-Sc (Sc_Lipo) to enhance its delivery efficiency. The findings demonstrate that both AD-Sc and Sc_Lipo effectively reduce reactive oxygen species levels in UV-damaged human fibroblasts, upregulate the expression of HAS1 and COL1, and inhibit MMP2. Moreover, it is discovered that reverse electrodialysis (RED)-driven iontophoresis improves the intradermal delivery of Sc_Lipo, as validated in an ex vivo porcine skin. Finally, in an in vivo UV-induced wrinkling mice model, the Lipo+RED group shows noticeable skin photoaging improvements. This study provides additional evidence that a combined intradermal delivery system for AD-Sc may represent a viable therapeutic approach for mitigating and preventing photoaging in clinical settings. AD-Sc exhibits anti-photoaging effects by scavenging UV-induced reactive oxygen species, upregulating HAS1 and COL1 alpha 1 genes, and downregulating MMP2 expression. Liposome and reverse electrodialysis-driven iontophoresis facilitate AD-Sc penetration into the epidermis and its delivery to UV-damaged cells in the dermis. Intradermal delivery of AD-Sc is more effective in mitigating photoaging than passive delivery onto the skin.image