8.5.1.1　Hyaluronic acid

Hyaluronic acid（HA）is a linear polysaccharide inherent in the human body，particularly abundant in the extracellular matrix.It has excellent biocompatibility，degradability，non-immunogenicity and low toxicity.HA can enhance the penetration of small molecule drugs（e.g.，diclofenac，ibuprofen，clindamycin and cyclosporine），and be modified on the surfaces of macromolecules and NPs to enhance their transdermal ability as well.For example，the conjugate of HA and human growth hormone（hGH）penetrates the skin of mice more strongly than free hGH.Conjugation of HA and nano-alkylene oxide Ce6 particles can also significantly promote the transdermal effect.HA plays the role of penetration enhancer mainly through the following mechanisms：①increasing the hydration of the stratum corneum，loosening the lipid bilayer，and making the hydrophilic drug more permeable；②changing the keratin in the stratum corneum from α-helix to β-sheet，making the lipid bilayer disordered；③relying on HA receptors expressed on living skin cells（e.g.，keratinocytes and fibroblasts）which are probably involved in the active transport of HA and the binding drugs.(https://www.daowen.com)