In vitro and in vivo biocompatibility of chitosan-xanthan polyionic complex

A novel hydrogel, CHITOXAN(TM) (CH-X), has po-tential as a vehicle for cont rolled drug delivery. The hydrogel is obtained by complexation of two polys accharides, chitosan and xanthan. In the present work we investigated the b iocompatibility of the complex using in vitro and in vivo models. The cytot oxic effects of CH-X microspheres as well as their degradation products at different concentrations were assessed on fibroblasts (fibroblast cell line L-929) using 3-(4,5-dimethylthiazole-2yl)-2,5-triphenyl tetrazolium) (MTT) . The test is based on mitochondrial dehydrogenase cell activity as an indi cator of cell viability. Interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) cytokines as well as nitric oxide (NO) production by macrophages (macrophage cell line J-774) were examined as indicators of cell activation. In vivo biocompatibility assessment was performed for 1 to 12 weeks. This study was performed using tablets obtained after compressio n of CH-X particles implanted at the subcutaneous level in male Wistar rats . CH-X biocompatibility and degradation were investigated using histologica l studies. Light and transmission electron microscopy (TEM) analyses were u sed to determine the foreign-body reaction and phagocytosis of the implants by macrophages. Fibroblast exposition to CH-X particles and degradation pr oducts did not show cytotoxic effects as measured by MTT test. TNF-alpha pr oduction was dependent on CH-X particles concentration, whereas IL-1 beta p roduction was found to be dose independent. CH-X extract products stimulate d TNF-alpha secretion when used at the highest concentration (10 mg/mL), no tably after 28 days' degradation time. No effect was observed on IL-1 beta production when CH-X extracts were used in comparison to the control. The e ffects of CH-X particles on NO secretion were similar as on TNF-alpha. Hist ological studies showed that CH-X tablets broke down into particles which p rogressively degraded into smaller fragments. A significant fraction of the fragments was ingested by the macrophages after 12 weeks of implantation. Light microscopy studies showed a weak foreign-body reaction as a function of time and the fibrous layer thickness decreased with time of implantation . (C) 2000 John Wiley & Sons, Inc. J Biomed Mater Res, 51, 107-116, 2000.