Evaluation of a highly skin permeable low-molecular-weight protamine conjugated epidermal growth factor for novel burn wound healing therapy.
We evaluated the laser induced burn wound healing efficacy of a recombinant low-molecular-weight protamine conjugated epidermal growth factor (rLMWP-EGF). rLMWP-EGF was prepared by genetically combining LMWP with the N-terminal sequence of EGF; we obtained a homogeneous modified EGF without reduced biological activity. Because of the protein transduction domain of LMWP, rLMWP-EGF showed enhanced drug penetration across artificial skin constructs and excised mouse skin layers versus EGF and showed significantly improved burn wound healing efficacy, with accelerated wound closure and minimized eschar and scar formation, compared with EGF or no treatment. Histological examination also revealed that rLMWP-EGF permeated through the intact skin around the wound and facilitated residual epithelial cell proliferation in an integrated manner to reform an intact epidermis. Radiofrequency microwound formation was effective for reducing large hypertrophic scars formed after severe laser burning by collagen remodeling but rLMWP-EGF did not show a meaningful synergistic effect in burn scar reduction. However, rLMWP-EGF was helpful for forming skin with a more normal appearance and texture. Thus, rLMWP-EGF demonstrated therapeutic potential as a novel topical burn wound healing drug with no obvious toxic effect.
['Lee|Ji Hae|JH|', 'Bae|Il-Hong|IH|', 'Choi|Jin Kyu|JK|', 'Park|Jin Woo|JW|']
D000818:Animals D002056:Burns D049109:Cell Proliferation D004815:Epidermal Growth Factor D005260:Female D006801:Humans D008297:Male D051379:Mice D008807:Mice, Inbred BALB C D011479:Protamines D011817:Rabbits D011993:Recombinant Fusion Proteins D012867:Skin D012869:Skin Absorption D014945:Wound Healing
permeability conjugation wound healing epithelial delivery/permeability peptide delivery percutaneous permeation enhancers protein delivery transdermal drug delivery