| Autor: |
Chellat, Fatiha, Tabrizian, Maryam, Dumitriu, Severian, Chornet, Esteban, Magny, Pierre, Rivard, CharlesHilaire, Yahia, LHocine |
| Zdroj: |
Journal of Biomedical Materials Research; July 2000, Vol. 51 Issue: 1 p107-116, 10p |
| Abstrakt: |
A novel hydrogel, CHITOXANTMCHX, has potential as a vehicle for controlled drug delivery. The hydrogel is obtained by complexation of two polysaccharides, chitosan and xanthan. In the present work we investigated the biocompatibility of the complex using in vitroand in vivomodels. The cytotoxic effects of CHX microspheres as well as their degradation products at different concentrations were assessed on fibroblasts fibroblast cell line L929 using 34,5dimethylthiazole2yl2,5triphenyl tetrazolium MTT. The test is based on mitochondrial dehydrogenase cell activity as an indicator of cell viability. Interleukin1β IL1β and tumor necrosis factorα TNFα cytokines as well as nitric oxide NO production by macrophages macrophage cell line J774 were examined as indicators of cell activation. In vivobiocompatibility assessment was performed for 1 to 12 weeks. This study was performed using tablets obtained after compression of CHX particles implanted at the subcutaneous level in male Wistar rats. CHX biocompatibility and degradation were investigated using histological studies. Light and transmission electron microscopy TEM analyses were used to determine the foreignbody reaction and phagocytosis of the implants by macrophages. Fibroblast exposition to CHX particles and degradation products did not show cytotoxic effects as measured by MTT test. TNFα production was dependent on CHX particles concentration, whereas IL1β production was found to be dose independent. CHX extract products stimulated TNFα secretion when used at the highest concentration 10 mgmL, notably after 28 days degradation time. No effect was observed on IL1β production when CHX extracts were used in comparison to the control. The effects of CHX particles on NO secretion were similar as on TNFα. Histological studies showed that CHX tablets broke down into particles which progressively 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 foreignbody reaction as a function of time and the fibrous layer thickness decreased with time of implantation. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res, 51, 107–116, 2000. |
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