Antitumor Effect of Quercetin Loaded Chitosan Nanoparticles on Induced Colon Cancer in Wistar Rats

Purpose: This study was aimed to evaluate the sitespecific drug delivery of 5FU with chitosan (CS) as a carrier and quercetin (Qu) against induced colon cancer in Wistar rats. lt;span style= textdecoration: underline; gt;Methods: Crosslinked CSQu nanoparticles (NPs) were prepared by ionotropic gelation method. Physicochemical characterization of NPs was performed by Fouriertransform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), in vitro drug release, and drug loading efficiency (LE). 1, 2Dimethylhydrazine (DMH) and dextran sulfate sodium (DSS) were applied to induce adenocarcinoma tumors on inbred male Wistar rats’ colon. The treatment group of rats was administered through enema with NPs dispersion. Hematoxylin and eosin staining were performed to the histopathological examination of tumors. Results: Zeta potential and particle size for NPs were +53.5 ± 5 mV and 179 ± 28 nm, respectively. About 96% Qu LE was obtained with a maximum release of 5.63 ±1.59% and 4.62 ± 1.33% after 24 hours in PB solution with pH values of 6 and 7.4, respectively. The numbers of 8 to 21 tumors were observed in all rats administered with DMH and DSS. Significantly decreasing of microvascular density and mitosis count was detected in the treatment group in comparison with cancerous group (P = 0.032 for the former compared to P = 0.016 for the later), respectively. Furthermore, the treatment group showed a high apoptosis rate (P = 0.038). Conclusion: The developed Quloaded CS NPs were good candidates for sitespecific and sustained drug release in enema treatment. Decreasing of microvascular density and mitosis count, along with increasing the apoptosis percent in the treatment group proved that the NPs could have promising results in sitespecific and sustained drug delivery against colorectal cancer.