Preparation and Administration of a Controlled-Release Delivery System of Chitosan Hydrogel loaded with Methadone and Piroxicam in Experimental Defect of Tibial in Rats; Histopathological Evaluation

Abstract

Purpose: In this study, a controlled-release drug delivery system loaded with piroxicam and methadone was synthesized and used subcutaneously in rats with experimental tibial defect, and healing were assessed histopathologically. Materials and Methods: For this purpose, 100 adult female rats were randomly divided into five equal groups; control group, chitosan group, piroxicam group, methadone group, and piroxicam-methadone group. The morphological structure of the synthesized drug systems was studied by scanning electron microscope. In addition, the structure of the hydrogels was investigated by Fourier transform infrared spectroscopy and while releasing the hydrogels' gelation time, the release of piroxicam and methadone from the hydrogels was evaluated in vitro. Results: Histological results of the 3rd day of the study showed the lowest extent and severity of inflammation in the chitosan, piroxicam, and piroxicam-methadone groups, while on the 7th day, tissue inflammation and the extent of bleeding were lower in the piroxicam, methadone, and piroxicam-methadone groups than in the other groups. Evaluation of new bone formation on day 21 showed that the chitosan, piroxicam, and methadone groups had better repair than the other groups. Conclusion: It seems that in the control group that did not receive any treatment intervention, following the experimental bone defect, the highest inflammatory response was observed in histological examination and finally the weakest bone repair. On the other hand, the presence of piroxicam, methadone, and chitosan in the piroxicam-methadone group (all of which have anti-inflammatory effects) also seems to have a negative effect on the repair.