Abstract
Cancer was ranked as the second leading cause of death, and colon cancer is recognized as third most common cancer worldwide with high morbidity and mortality. Chemotherapeutic drugs act on normal and cancerous cells similarly; therefore, they have various adverse side effects. The present study was undertaken synergistic effect of anticancer phytochemicals gallic acid isolated from amla fruit and quercetin isolated from peels of pomegranate fruit incorporated into chitosan have been used as nanoplatform for the targeted delivery to colorectal cancer. The study was evaluated using cytotoxic assay such as MTT assay and in-vivo studies were performed on DMH induced colorectal cancer in Wistar rats. Identification of the biomolecules was performed by using different chromatographic and spectroscopic techniques, as 1H NMR, GC-MS, LC-MS, and HPTLC. Characterization of chitosan (CS) nanoparticles carried out by using X-ray diffraction (XRD) Differential scanning calorimetry (DSC), Scanning Electron Microscope (SEM), entrapment efficiency and In vitro drug release confirmed successful encapsulation of biomolecules into nanoparticles. A significant change in aberrant crypt foci (ACF) in CS nanoparticles compared to polyherbal extract were observed, with a decrease in the colonic glutathione, catalase and superoxide dismutase levels and values differed significantly (P < 0.005).
Highlights
Our results provide a rationale for using hydrophilic mucoadhesive chitosan for the development of a nanoparticles by using gallic acid and quercetin biomolecules that significantly accumulates in the colonic mucosa, tumor targeting, high efficacy in Colorectal cancer (CRC) rats, enhancement of bioavailability on likewise achieving the sustained release.(Pham, Sakoff, Van Vuong, Bowyer, & Scarlett, 2018)
Poloxamer 407 from BASF, Chitosan 90% dda obtained from CIFT Cochin, GMO from Mohini organics, gallic acid and quercetin purchased from Loba Chemie., 10% fetal bovine serum (Invitrogen Life Technologies USA), McCoy’s 5A medium (Fisher Scientific, Waltham, USA)
All GC-MS data correlates the structure of the fraction A16 as gallic acid
Summary
Colorectal cancer (CRC) is well-known malady issues in worldwide with high dismalness and mortality cancer causes fourth common reason deaths in every year. (Gumireddy et al, 2019) the conventional treatments such as chemotherapy and radiotherapy used in advanced stages but these therapies are invasive with serious side effects and development of drug resistance. (Schirrmacher, 2019) In this current work a great efforts for the discovery and development of nanoformulation based on natural products for CRC treatment. (Frazier et al, 2018) Various researchers have recommended that utilization of fruits that diminishes the danger of colorectal cancer. (He, Chen, Rojanasakul, Rankin, & Chen, 2016) In our study natural biomolecules as gallic acid (phenolic) isolated from amla fruit (Emblica officinalis) and quercetin (flavonoid) from peels of pomegranate fruit (punica granatum), here specific endeavors to assess the therapeutic role of these active constituents rather than using whole extract of both fruits (Elfalleh et al, 2012; Gupta, Dhawan, & Gupta, 2019) A number of studies have demonstrated that many pharmacological and biochemical pathways altered by gallic acid because of its strong antioxidant and anticancer properties (Ambrosone et al, 2020; Sánchez-Carranza et al, 2018) According to the bibliometric analysis on the Web of Science, quercetin has become a research hotspot used as a nutraceutical effective in the treatment of cancers.(Rauf et al, 2018; Zarei, Hamzeh-Mivehroud, Benvenuti, Ustun-Alkan, & Dastmalchi, 2017) gallic acid and quercetin has limited application in the pharmaceutical field because of its low solubility, low bioavailability and instability. As to upgrade the focusing on targeting delivery, to improve solubility and bioavailability of above biomolecules newer nanoparticles have emerged in recent years, in the field of research and development.(Aghapour et al, 2018; Chen, Lee, Huang, & Chang, 2016) Motivated by this rationale we reported design and fabrication of biomolecules in polymeric nanoparticles they having the ability to protect, entrap, attach or release chemotherapeutic entities into their matrices, with beneficial properties for human health and wellness.(Kumar, Gajbhiye, Paknikar, & Gajbhiye, 2019) Chitosan (CS) is a natural renewable polymer and GMO as a lipid phase has received increasing attention as adhesive nature and passively target with cancerous cells; provide a controlled release drug delivery. Our results provide a rationale for using hydrophilic mucoadhesive chitosan for the development of a nanoparticles by using gallic acid and quercetin biomolecules that significantly accumulates in the colonic mucosa, tumor targeting, high efficacy in CRC rats, enhancement of bioavailability on likewise achieving the sustained release.(Pham, Sakoff, Van Vuong, Bowyer, & Scarlett, 2018)
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