A fibrin gel loaded with chitosan nanoparticles for local delivery of rhEGF: preparation and in vitro release studies

Abstract

Recombinant human epidermal growth factor (rhEGF) is known to stimulate cell proliferation and accelerate wound healing. Direct delivery of rhEGF at the wound site in a sustained and controllable way without loss of bioactivity would enhance its biological effects. The aim of this study was to prepare a novel local delivery system for the sustained and controllable release of rhEGF, a fibrin gel loaded with chitosan nanoparticles. First, rhEGF-loaded chitosan nanoparticles were prepared and characterized, and these showed an ability to protect rhEGF from proteolysis. The prepared nanoparticles were then incorporated into a fibrin gel matrix during polymerization. In vitro release studies showed that the fibrin gel loaded with rhEGF/chitosan nanoparticles could achieve a more sustained release of rhEGF than either chitosan nanoparticles or an unloaded fibrin gel. Additionally, the release rate could be controlled by altering the contents of fibrinogen and thrombin in this composite delivery system. The bioactivity of the released rhEGF was determined by assessing its ability to stimulate the proliferation of BALB/c 3T3 cells, and the results showed that rhEGF bioactivity was not affected during the preparation process and could be maintained for at least 7 days. This novel delivery system may have great potential applications in the local administration of rhEGF.