Amniotic Mesenchymal Stem Cells Metabolite Products (AMSC-MP) contain growth factors that benefit human health. This study aims to evaluate the use of transfersomal serum (Trans) with hyaluronic acid (HA) addition to deliver large molecules of AMSC-MP for skin regeneration. Trans is composed of L-α-phosphatidylcholine and surfactants, i.e., sodium cholate (SC) or stearylamine (SA), at the weight ratio of 85:15, prepared by the thin film method with or without HA addition. The results showed that HA addition increased the particle size of Trans-SA and Trans-SC, from 261.9 ± 1.9 and 105.3 ± 0.9 nm respectively, to 317.7 ± 9.1 and 144.3 ± 0.8 nm for Trans-SA-HA and Trans-SC-HA. In contrast, no significant changes in the zeta potential occurred. The relative deformability indexes of Trans-SA, Trans-SA-HA, Trans-SC, and Trans-SC-HA compared to liposome were 0.43 ± 0.09, 0.46 ± 0.09, 1.58 ± 0.17, and 1.40 ± 0.17 respectively. The addition of HA successfully increases the in vivo skin hydration, collagen density, and number of fibroblast cells, reflecting the capacity for skin regeneration in UV-induced aged mice. Furthermore, no erythema or skin rash was observed at the 24-hour post-topical application sites. AMSC-MP transfersomal serum with HA addition successfully enhanced skin regeneration and proved safe during the in vivo study using UV aging-induced mice models, thereby enabling its potential use as skin-aging therapy.
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