title: Evaluation of a highly skin permeable low-molecular-weight protamine conjugated epidermal growth factor for novel burn wound healing therapy.
abstract: 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.
authors.affiliation: Amorepacific Corporation R&D Center, Giheung-gu, Yongin-si, Gyeonggi-do, 446-729, Republic of Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Lee
authors.forename: Il-Hong
authors.initials: IH
authors.lastname: Bae
authors.forename: Jin Kyu
authors.initials: JK
authors.lastname: Choi
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D000818:Animals; D002056:Burns / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011479:Protamines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012869:Skin Absorption; D014945:Wound Healing / Q000187:drug effects
chemical_list: D011479:Protamines; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor
keywords: conjugation; epithelial delivery/permeability; peptide delivery; percutaneous; permeability; permeation enhancers; protein delivery; transdermal drug delivery; wound healing