Transdermal Co-Delivery of Urea and Recombinant Human Growth Hormone

Background: Urea with super-hydrating and moisturizing properties is mainly used as an adjunctive treatment of diseases associated with dry skin. In this regard, the recombinant human growth hormone (rhGH) with rejuvenating properties is used as a base material in beauty creams. Although urea easily passes through the skin, the epidermal skin barrier restricts the passage of hGH due to its size. Objective: in this research, in order to solve this problem, hydroxy propyl-beta cyclodextrin (HP-β-CD) is used as a soluble chemical enhancer. Material and Methods: UV and circular dichroism spectroscopy were used for the investigation of structural modification. The permeation process was studied in vitro on rat skin using vertical Franz diffusion cells. Enzyme-linked immunosorbent assay were used for rhGH activity assessment and evaluation of transdermal delivery. Results: First, due to the denaturing effects of urea on proteins its concentration was optimized to maintain biological structure and protein activity. UV spectroscopy and CD data proved that the secondary structure of rhGH is preserved in the presence of urea (0.5-2 M) and HP-β-CD, which elevates urea and rhGH permeation. Maximum permeability was observed at 120 min after sampling (1424.35 ng.ml.cm-2), which was much higher than the control. Using a higher concentration of urea in the formulation will significantly decrease the level of rhGH delivery. Conclusion: According to results, this strategy can be considered as a successful method for enhanced Co-delivery of rhGH and urea.