Anti-tumor Effect of Quercetin Loaded Chitosan Nanoparticles onInduced Colon Cancer in Wistar Rats

This study was aimed to evaluate the site-specific drug delivery of 5-FU with chitosan(CS) as a carrier and quercetin (Qu) against induced colon cancer in Wistar rats. Cross-linked CS-Qu nanoparticles (NPs) were prepared by ionotropic gelation method.Physicochemical characterization of NPs was performed by Fourier-transform infrared (FTIR)spectroscopy, dynamic light scattering (DLS), in vitro drug release, and drug loading efficiency(LE). 1, 2-Dimethylhydrazine (DMH) and dextran sulfate sodium (DSS) were applied to induceadenocarcinoma tumors on inbred male Wistar rats’ colon. The treatment group of rats wasadministered through enema with NPs dispersion. Hematoxylin and eosin staining were performedto the histopathological examination of tumors. 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 21tumors were observed in all rats administered with DMH and DSS. Significantly decreasing ofmicrovascular density and mitosis count was detected in the treatment group in comparison withcancerous 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). The developed Qu-loaded CS NPs were good candidates for site-specific andsustained drug release in enema treatment. Decreasing of microvascular density and mitosiscount, along with increasing the apoptosis percent in the treatment group proved that the NPscould have promising results in site-specific and sustained drug delivery against colorectal cancer.