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


OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.


CONCLUSIONS
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.
a Nanomedicine and Biomaterial Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran .|b Nano Alvand Co., Avicenna Tech Park, Tehran University of Medical Sciences , Tehran , Iran .
Mirhamed
M
Hajimiri
a Nanomedicine and Biomaterial Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran .|c Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran .
Sheida
S
Shahverdi
a Nanomedicine and Biomaterial Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran .
Mohammad Amin
MA
Esfandiari
d Endocrinology and Metabolism Research Center (EMRC), Tehran University Medical Sciences , Tehran , Iran .
Bagher
B
Larijani
a Nanomedicine and Biomaterial Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran .|c Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran .
Fatemeh
F
Atyabi
e Department of Pathology, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran .
Afsaneh
A
Rajabiani
f Department of Pharmacology, Faculty of Medicine , Tehran University of Medical Sciences , Tehran , Iran , and.
Ahmad Reza
AR
Dehpour
g Department of Medicinal Chemistry, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
Mohsen
M
Amini
a Nanomedicine and Biomaterial Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran .|c Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences , Tehran , Iran .
Rassoul
R
Dinarvand
D000818:Animals; D001458:Bandages; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
D011108:Polymers; D011994:Recombinant Proteins; C514968:carboxymethyl-chitosan; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D004815:Epidermal Growth Factor; D048271:Chitosan
Chitosan; molecular weight determination; protein delivery; rhEGF; wound healing