PEG-g-chitosan thermosensitive hydrogel for implant drug delivery: cytotoxicity,in vivodegradation and drug release

Abstract

Thermosensitive hydrogels based on chitosan are of great interests for injectable implant drug delivery. The poly(ethylene glycol)-grafted-chitosan (PEG-g-CS) hydrogel was reported as a potential thermosensitive system. The objective of the present study is to evaluate the cytotoxicity, in vivo degradation and drug release of PEG-g-CS hydrogel. Cytotoxicity was evaluated using L929 murine fibrosarcoma cell line. Degradation and drug release in vivo were investigated by subcutaneous injection of the hydrogel into Sprague-Dawley rats. PEG-g-CS polymer exhibits no significant cytotoxicity when its concentration is less than 3 mg mL(-1). After being implanted, PEG-g-CS hydrogel maintains its integrity for two weeks and collapses, merging into the tissue, in the third week. It causes moderate inflammatory response but no fibrous encapsulation around the hydrogel is found. The hydrogel presents a three-week sustained release of cyclosporine A with no significant burst release in vitro and produces the effective drug concentration in blood for more than five weeks in vivo, performing almost the same bioavailability to chitosan/glycerophosphate hydrogel. Further modifications of PEG-g-CS hydrogel might be necessary to modulate the degradation and to mitigate the fluctuations in blood drug concentration.

Blended Chitosan Paste for Infection Prevention: Preliminary and Preclinical Evaluations

“…The chitosan/PEG hydrogel literature has reported acceptable biocompatibility [14,25,26]. The results found from this testing performed on chitosan/PEG pastes are comparable to the various reported chitosan hydrogels [8,17,24].…”

“…The results found from this testing performed on chitosan/PEG pastes are comparable to the various reported chitosan hydrogels [8,17,24]. Results found from in vivo studies vary from immediate inflammation, tissue encapsulation from an implanted hydrogel, moderate inflammation from chitosan/ PEG devices, to minimal inflammatory response from various hydrogels [8,14,15,23,26]. The evaluated blended chitosan/PEG paste formulations in our study experienced similar cellular responses to that of the neutral 1% chitosan sponge in vitro, which is comparable to the aforementioned studies.…”

“…Although other chitosan/PEG hydrogels have been shown to release cyclosporine A and bovine serum albumin in a steady release, these hydrogels were not tested for the activity or release of proteins in vitro [5,14,25]. Neutral chitosan and chitosan/PEG combination sponges have been shown to release an initial burst release of vancomycin at 7% and 16%, respectively, but decreased at longer time points [17].…”

Development and Characterization of a New Endoscopic Drug Eluting Platform with Proven Efficacy in Acute and Chronic Experimental Colitis

“…Morphologically, our hydrogel presents a macroporous (pore diameters of greater than 50 nm) interconnected network that can be the matrix for cell ingrowth as well as nutrients and waste flow, essential characteristics for cell survival within the hydrogel. This platform is less vulnerable to matrix transformations due to osmotic pressure or tissue extrusion, which is an advantage for a controlled drug release of the hydrogel 19 . Different kinetic models were studied with the results obtained from the drug release experiments.…”

Development of a Layer-by-Layer Assembled Film on Hydrogel for Ocular Drug Delivery

“…Therefore, the curative effects of ophthalmic drug would be enhanced. Hydrogel is a kind of attractive drug carriers because of its biocompatibility [5][6][7]. Moreover, hydrogel had good transparency, which made it have wide applications in ophthalmology [8][9][10][11][12].…”