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Adv Pharm Bull. 2019;9(3): 409-415.
doi: 10.15171/apb.2019.048
PMID: 31592135
PMCID: PMC6773937
Scopus ID: 85070465414
  Abstract View: 501
  PDF Download: 414

Research Article

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

Jalil Rashedi 1, Amir Ghorbani Haghjo 2 * , Mehran Mesgari Abbasi 3 ORCID logo, Ali Dastranj Tabrizi 4, Shadi Yaqoubi 5, Davoud Sanajou 1, Zahra Ashrafi Jigheh 1, Ali Namvaran 6, Ali Mohammadi 7, Jalal Mohammadi Khoshraj 8, Behzad Baradaran 9 * ORCID logo

1 Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Women’s Reproduction Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
5 Biotechnology Research Center and Faculty Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
6 Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
7 Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense C, Denmark.
8 Department of Analytical Chemistry, Chemistry Faculty, Tabriz University, Tabriz, Iran.
9 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

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.

Keywords: Anti-tumor, Chitosan, Colon, Nanoparticles, Quercetin, Rats, Wistar
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