title: Acceleration of diabetic-wound healing with PEGylated rhaFGF in healing-impaired streptozocin diabetic rats.
abstract: Molecular modification with polyethylene glycol (PEGylation) is an effective approach to improve protein biostability, in vivo lifetime and therapeutic potency. In the present study, the recombinant human acid fibroblast growth factor (rhaFGF) was site-selectively PEGylated with 20 kDa mPEG-butyraldehyde. Mono-PEGylated rhaFGF was purified to near homogeneity by Sephadex G 25-gel filtration followed by a Heparin Sepharose TM CL-6B affinity chromatography. PEGylated rhaFGF has less effect than the native rhaFGF on the stimulation of 3T3 cell proliferation in vitro; however, its relative thermal stability at normal physiological temperature and structural stability were significantly enhanced, and its half-life time in vivo was significantly extended. Then, the physiological function of PEGylated rhaFGF on diabetic-wound healing was evaluated in type 1 diabetic Sprague Dawley rats. The results showed that, compared with the group of animal treated with native rhaFGF, the group treated with PEGylated rhaFGF exhibited better therapeutic efficacy with shorter healing time, quicker tissue collagen generation, earlier and higher transforming growth factor (TGF)-β expression, and dermal cell proliferation. In addition, in vivo analysis showed that both native and PEGylated rhaFGF were more effective in the wound healing in the diabetic group compared with the nondiabetic one. Taken together, these results suggest that PEGylation of rhaFGF could be a more effective approach to the pharmacological and therapeutic application of native rhaFGF.
authors.affiliation: Key Laboratory of Biotechnology and Pharmaceutical Engineering of Zhejiang Province, Wenzhou Medical College, Wenzhou, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Huang
authors.forename: Meifei
authors.initials: M
authors.lastname: Lu
authors.forename: Guanghui
authors.initials: G
authors.lastname: Zhu
authors.forename: Hongchang
authors.initials: H
authors.lastname: Gao
authors.forename: Liyun
authors.initials: L
authors.lastname: Xie
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhang
authors.forename: Chaohui
authors.initials: C
authors.lastname: Ye
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Chuanchuan
authors.initials: C
authors.lastname: Sun
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004355:Drug Stability; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D012867:Skin / Q000293:injuries* / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D011994:Recombinant Proteins; D016220:Fibroblast Growth Factor 1; D011092:Polyethylene Glycols