Preparation, Characterization and Efficacy of Hyaluronic Acid-Modified Two Targeted Liposomes for Ectoin Delivery to the Skin

In biomedicine and cosmetics, skin-targeted drug delivery is crucial yet challenging due to the skin complex barrier. Low molecular weight hyaluronic acid (HA) shows targeting ability as it can bind to CD44 receptors overexpressed on fibroblasts. Two types of targeted liposomes were developed in this study, covalently modified hyaluronic acid-ectoine liposome (HA-ECT-LPs) and non-covalently modified hyaluronic acid-chitosan-ectoine liposome (HA-CS-ECT-LPs). DSPE can stabilize liposomes through the interaction of low molecular weight HA chains in bilayer, and can be covalently modified on the surface of liposomes after coupling with HA. The non-covalently modified liposomes adsorbed HA electrostatic onto the surface of chitosan-coated ectodoin liposomes, which can easily and quickly form multilayer liposomes and delay drug release. The sizes, PDIs, and zeta potentials particle sizes of HA-ECT-LPs and HA-CS-ECT-LPs were determined to be 280 ± 4   nm and 232 ± 7   nm, PDI were 0.30 ± 0.04 and 0.50 ± 0.11, Zeta potential were -24 ± 2   mV and -13 ± 1   mV, respectively. The 90 days stability tests showed HA-ECT-LPs and HA-CS-ECT-LPs has good stability, ΔBS were less than 0.5%. Drug release test showed that HA-ECT-LPs and HA-CS-ECT-LPs with slower release than ectoine liposomes in vitro . Skin permeation proved that compared with ectoine liposomes, the cumulative release amount of HA-ECT-LPs and HA-CS-ECT-LPs increased by 41% and 31%, and the cumulative retention amount increased by 21% and 10%, respectively. Cell experiments demonstrated that both types of liposomes have excellent targeting to fibroblasts. The evaluation of the efficacy of liposomes on human skin indicated that for the essence liquids of HA-ECT-LPs and HA-CS-ECT-LPs, after 7 days, the skin water content increased by 2.51 times and 2.56 times respectively, and the transepidermal water loss (TEWL) decreased by 1.69 times and 2.45 times respectively. After 30 days, the skin elasticity increased by 2.88 times and 2.29 times respectively. Overall, these liposomes offered great potential for skin delivery of ectoine, offering a promising approach for skin health applications.