Novel chitosan based nanoparticulate delivery system for egf

Samaneh Montazeri,1 Zohreh mohammadi,2,* Mahboobeh nazari,3 Hanieh jafary,4

1. Department of Biology, Science and Research Branch,Islamic Azad University, Tehran ,Iran.
2. School of Pharmacy- International campus, Iran University of Medical Sciences, Tehran, Iran.
3. Monoclonal Antibody Research Center ,Avicenna Research Institute,Tehran,Iran.
4. Department of Biology, Science and Research Branch,Islamic Azad University, Tehran ,Iran.

Abstract

Introduction

Epithelial growth factor (egf) is a single-chain polypeptide containing 53 amino acid residues (mw = 6,045) and three disulfide bridges that are required for biological activity. this polypeptide stimulates the proliferation of epidermal cells as well as other cell types such as fibroblasts and endothelial cells and so can accelerate wound healing process. many studies have investigated the application of egf for the treatment of wounds. however ,¬due to its susceptibility to proteolysis and denaturation ,¬and also relatively short half-life, maintaining an effective topical concentration at the wound site during certain period of time is very difficult. therefore, the development of a suitable delivery system for egf to achieve a sustained release and improve its bioavailability is necessary. in recent years, polymeric nanoparticles have attracted considerable attention as potential drug-delivery vehicles. chitosan (cs), a linear cationic polysaccharide composed of deacetylated beta-1,4-d-glucosamine, has been considered as a candidate pharmaceutical material for biomolecular delivery, based on its unique features such as biocompatibility, biodegradablity ,mucoadhesive behavior ,¬non-toxicity ,and anti-inflammatory characteristics. moreover, chitosan itself has beneficial effects on wound healing. the aim of this study was to prepare a novel delivery system for protection and controllable release of rhegf through chitosan nanoparticles for using in topical formulation in future.

Methods

- size, zeta potential and poly dispersity index of nanogels were evaluated by nanozetasizer - loading efficiency pattern of rhegf from the chitosan nanogel was measured by hplc technique - release pattern of rhegf from the chitosan nanogel was measured by hplc technique - the effect of egf nanogels,and chitosan on growth rate of cells were determined by evaluating their effects on proliferation of human melanoma skin cancer cells (a375).

Results

Nanogels containing the ratio of 2:1 and 6:1 (chitosan to protein) revealed loading efficiency of 90% and 97.4% respectively. moreover, they were able to release 80% and 60% of the protein after 24 hours. the cell viability studies indicated significant growth induction in both ratios, while stability of protein by both of these nanogels was well preserved.

Conclusion

According to the findings of this study, chitosan nanogels containing rhegf in optimal ratios may be suitable candidates for dermal formulation, with regenerative purposes.

Keywords

Nanogel chitosan - epidermal growth factors - wound healing