Abstract
Purpose: 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. Methods: 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 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 Qu-loaded CS NPs were good candidates for site-specific 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 site-specific and sustained drug delivery against colorectal cancer.
Highlights
Colorectal cancer is the second common cancer and the fourth cause of cancer deaths in the world
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
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 site-specific and sustained drug delivery against colorectal cancer
Summary
Colorectal cancer is the second common cancer and the fourth cause of cancer deaths in the world. Some NPs adopting chemotherapy drugs[7,8,9] have been investigated whose drug delivery behavior have been considered and the satisfactory results of the effect of them on the target as well as reduced drug complications was obtained. Thanks to their low toxicity and greater biocompatibility, the utilization of natural compounds as Rashedi et al carriers in drug delivery has attracted more attention.[10,11] Chitosan (CS), as the only naturally occurring positivecharge polysaccharide, has remarkable properties including high bioavailability, super biodegradability, high biocompatibility, non-toxicity, etc.[12,13] In addition to able to carry a variety of hydrophilic and hydrophobic drugs, this polymer has the ability to open the intercellular tight junctions of epithelia
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