[Show abstract][Hide abstract] ABSTRACT: This study was designed to develop a skin permeable recombinant low-molecular-weight protamine (LMWP) conjugated epidermal growth factor (EGF) (rLMWP-EGF) by linking a highly positive charged LMWP to the N-terminal of EGF through genetic recombination. We evaluated its biological activity, skin permeability, and wound healing efficacy in vivo. The cDNA for rLMWP-EGF was prepared by serial polymerase chain reaction for encoding amino acids of LMWP to the vector for EGF. After expression and purification, recombinant EGF site-specifically conjugated with LMWP was obtained. The in vitro cell proliferation activity was well preserved after LMWP conjugation and was comparable to that of rEGF. rLMWP-EGF showed markedly improved permeability through the three-dimensional artificial human skin constructs, and the cumulative permeation of rLMWP-EGF across the excised mouse skin was about 11 times higher than that of rEGF. Topically applied rLMWP-EGF significantly accelerated the wound closure rate in full thickness as well as a diabetic wound model most probably due to its enhanced skin permeation. These findings demonstrate the therapeutic potential of rLMWP-EGF as a new topical wound healing drug and the site-specific conjugation of LMWP to peptides or proteins by genetic recombination as a useful method for preparing highly effective biomedicines.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the ability of a novel radiofrequency (RF) microporation technology based on ablation of the skin barrier to enhance topical delivery of active ingredients
The influence of RF fluence and the molecular size of the absorbent on the permeation enhancement was confirmed by in vitro skin permeation study using Franz diffusion cells. The improved skin rejuvenation effects, such as depigmentation and anti-wrinkle effects, by enhanced topical delivery of α-bisabolol and epidermal growth factor (EGF) through the RF microchannels were investigated in photo-damaged skin.
The cumulative amounts of active ingredients through the RF microporated skin were significantly increased. Topically applied α-bisabolol after RF microporation induced rapid onset of skin whitening and significantly increased the ΔL-value of UVB-induced hyperpigmented melanin hairless mouse skin. In addition, wrinkle formation after topical application of EGF with RF microporation was significantly reduced and prevented after 12 weeks, and all parameters involving wrinkles in a replica analysis were similar to those in the negative control.
RF microporation enhances the topical delivery of active ingredients with high molecular weight or of small hydrophilic or lipophilic molecules. Thus, this technology can effectively improve photo-induced hyperpigmentation and wrinkle formation by enhancing topical delivery of active agents.
No preview · Article · Mar 2012 · Pharmaceutical Research