Hyaluronic acid-modified cationic nanoemulsion prepared by electrostatic self-assembly for improved specific targeting of keratinocytes and enhanced barrier repair efficacy

The expression of the Cluster of Differentiation 44 (CD44) receptor on the surface of keratinocytes provides a programmable target for localised precision drug delivery in the skin . The development of hyaluronic acid surface-modified ceramide cationic nanoemulsions (HA-CER-CNE) was based on electrostatic self-assembly between anionic hyaluronic acid (HA) and cationic ceramide nanoemulsions (CER-CNE). This carrier combines three functions: receptor-ligand-mediated endocytosis, high drug-loading capacity, and barrier repair. The subject under discussion here is an advancement on traditional ceramide formulations. The latter are limited by short skin retention times, low bioavailability, and unclear target specificity. The study found that HA-CER-CNE was significantly more endocytosed by HaCaT cells than CER-CNE. This was due to the specific binding of HA to the CD44 receptor, which was confirmed by confocal laser scanning microscopy (CLSM). An in vitro skin retention test demonstrated a 1.17-fold and 2.29-fold increase in skin retention of ceramide NP with HA-CER-CNE in comparison with CER-CNE and CER-suspension at 24 h. Furthermore, a cell scratch assay was employed to ascertain that HA-CER-CNE can further improve barrier damage. The cell migration rate of the HA-CER-CNE sample was 76.81 %, in comparison to 58.59 % for the CER-CNE sample. This indicates an enhancement of cell migration of 31.10 % in the former sample. The efficacy evaluation of HA-CER-CNE demonstrated that, incompared to CER-CNE and CER-suspension, HA-CER-CNE enhanced skin hydration by 1.62-fold and 4.13-fold, respectively, and reduced transdermal water loss (TEWL) by 1.75-fold and 4.23-fold, respectively, over a period of seven days. The findings demonstrate that HA-CER-CNE achieves precise delivery and retention of ceramides via a CD44-targeting strategy, exhibiting dual properties as both a drug carrier and bioactive agent.