Preparation of hydrogel embedded polymer-growth factor conjugated nanoparticles as a diabetic wound dressing

• Published in: Drug development and industrial pharmacy 2016, Vol.42 (5), p.707
• Main Authors: Hajimiri, Mirhamed, Shahverdi, Sheida, Esfandiari, Mohammad Amin, Larijani, Bagher, Atyabi, Fatemeh, Rajabiani, Afsaneh, Dehpour, Ahmad Reza, Amini, Mohsen, Dinarvand, Rassoul
• Format: Article
• Language: English
• Subjects: Animals; Bandages; Cell Line; Cell Proliferation - drug effects; Chitosan - analogs & derivatives; Chitosan - chemistry; Diabetes Mellitus, Experimental - drug therapy; Epidermal Growth Factor - chemistry; Epidermal Growth Factor - pharmacology; Fibroblasts - drug effects; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology; Male; Mice; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Polymers - chemistry; Polymers - pharmacology; Rats; Rats, Sprague-Dawley; Recombinant Proteins - chemistry; Recombinant Proteins - pharmacology; Wound Healing - drug effects
• ISSN: 1520-5762

Growth factors act in an integrated manner to promote the wound-healing process. However, probably due to early inactivation of these molecules in the wound site, their topical administration scarcely leads to a significant improvement in chronic wound repair. With the aim of identifying improved therapeutics, a sodium carboxymethyl chitosan-recombinant human epidermal growth factor conjugate (NaCMCh-rhEGF) was developed. It is believed that conjugation will protect rhEGF against proteolysis and will mediate rhEGF release by α-amylase. As hydrogels possess most of the desirable characteristics of an ideal dressing, we used our previously described chitosan-based hydrogel as a carrier for NaCMCh-rhEGF nanoparticles to make a novel wound dressing system. To evaluate the biological activity of NaCMCh-rhEGF and free rhEGF, the proliferation of fibroblasts was measured using a colorimetric assay. Additionally the stability of conjugated and free rhEGF against proteases was estimated. In vitro results revealed that the conjugated form exhibited more stability against proteolysis and also preserved its biological activity. Furthermore, in vivo studies were performed using an excision wound model on diabetic rats. After 15 d, the wound area in NaCMCh-rhEGF-hydrogel dressing group was significantly smaller than other groups and showed histological parameters equal to positive wound control group. A polymer conjugated rhEGF was developed that was more stable against proteases and reserved the biological activity of the drug. This dressing appears to be a competent candidate for chronic wound healing.