Transdermal delivery of hyaluronic acid -- human growth hormone conjugate.

Hyaluronic acid (HA) is one of the major components of extracellular matrix (ECM). Keratinocyte and fibroblast are known to have HA receptors in the skin. Fibroblast also has human growth hormone (hGH) receptors. In this work, HA-hGH conjugate was developed as a receptor mediated transdermal delivery system of protein drugs. HA-hGH conjugate was synthesized by specific coupling reaction between aldehyde modified HA and the N-terminal amine group of hGH. We could confirm the proliferative effect of HA on keratinocyte and fibroblast, and the biological activity of HA-hGH conjugate in fibroblast with an elevated expression level of phosphorylated Janus kinase 2 (p-JAK2). Interestingly, fluorescence microscopy clearly visualized the dramatically enhanced penetration of HA-hGH conjugate through the dorsal skin of mice after topical treatment with FITC labeled HA-hGH conjugate. According to pharmacokinetic analysis, HA-hGH conjugate appeared to be delivered through the skin into the blood stream possibly by the receptor mediated transdermal delivery. This work confirms the feasibility of using the HA-hGH conjugate as a model system for the receptor mediated transdermal delivery of protein drugs and their further exploitation for various cosmetic and tissue engineering applications.