The effect of epidermal growth factor (EGF) conjugated with low-molecular-weight protamine (LMWP) on wound healing of the skin

Jin Kyu Choi, Ji Hye Jang, Won Hee Jang, Jaekwan Kim, Il Hong Bae, Joonho Bae, Young Ho Park, Beum Joon Kim, Kyung Min Lim, Jin Woo Park

Research output: Contribution to journalArticlepeer-review

77 Scopus citations

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.

Original languageEnglish
Pages (from-to)8579-8590
Number of pages12
JournalBiomaterials
Volume33
Issue number33
DOIs
StatePublished - Nov 2012

Keywords

  • Epidermal growth factor
  • Low-molecular-weight protamine
  • Protein transduction domain
  • Topical delivery
  • Transdermal delivery
  • Wound healing

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