An Innovative Approach for Formulation of Rutin Tablets Targeted for Colon Cancer Treatment

Abstract

The aim of this study was the improvement of rutin solubility along with targeting its release to colon for effective treatment of colon cancer. Five formulations of compression-coated tablets were prepared with the same core composition including rutin-polyvinyl pyrrolidone K30 solid dispersion (rutin-PVP K30 SD) but differ in being coated with either frankincense alone or different combinations of frankincense with gelatin. The superior formula was selected based on the in vitro drug release then further evaluated in terms of physical properties and in vivo performance in dogs using X-ray. Moreover, in vitro cytotoxicity of rutin, rutin-PVP K30 SD, frankincense, and a mixture of rutin-PVP K30 SD with frankincense in a ratio representing their concentrations in the selected formula was assessed against human colon cancer (HCT-116) cell lines using sulforhodamine B assay. The formula (F4) with the coat consisted of 65%w/w frankincense and 35%w/w gelatin achieved acceptable in vitro controlled drug release. In vivo X-ray in dogs confirmed that F4 tablet could remain intact in the stomach and small intestine until reaching the colon. In vitro cytotoxicity revealed that mixture of rutin-PVP K30 SD with frankincense was more effective in arresting cancer cell growth than rutin or frankincense alone. Moreover, stability studies revealed that F4 tablets were physically and chemically stable. Thus, improving rutin solubility using solid dispersion technique and formulating it into frankincense-based compression-coated (F4) tablets would be a successful approach for colonic delivery of rutin with potential of improving therapeutic efficacy. Graphical Abstract

Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy

“…However, MIT and DOX caused significant shrinkage of PCa and BCa tumors, respectively, suggesting the anticancer capacity of such typical chemotherapeutic agents is generally higher than that of rapamycin and rutin (senomorphics) when used alone, especially in the experimental settings of our study. Although former studies reported the effectiveness of these agents in cancer treatments (Ismail et al, 2023 ; Yin et al, 2023 ), the virtual efficacy of each of these senomorphics may be dependent on a number of specified factors such as the pharmacological dose, cancer type, and administration schedule of anticancer regimens.…”

Role of natural products in tumor therapy from basic research and clinical perspectives

“…Nafees et al [36] showed that rutin in combination with silibinin produces synergistic anti-cancer effects on HT29 CRC cells by regulating expression of apoptosis, inflammation, and MAPK pathway proteins. Recently, a new colonic delivery method for rutin was studied by formulating rutin into frankincense-based compression-coated tablets and showed that the anti-cancer effect was improved [37]. Interestingly, network pharmacology and analysis of gene biological information showed that the potential intracellular signaling pathways of rutin in human SW480 cells may be associated with miRNAs-long noncoding RNAs (lncRNAs)-messenger RNAs-transcription factors [38].…”

Rutin Cocrystals with Improved Solubility, Bioavailability, and Bioactivities

“…Nanocrystal-loaded tablets dissolved completely within 30 min, while market tablets dissolved about 60% of rutin. , The solid dispersions of rutin were obtained by solvent evaporation at a weight ratio of 1:1. Rutin-PVP K30 SD exhibited a higher equilibrium solubility compared with pure rutin . Paczkowska et al obtained a rutin-β-cyclodextrin complex by cogrinding, and the solubility of rutin and the rutin-β-cyclodextrin complex was studied.…”

“…Rutin-PVP K30 SD exhibited a higher equilibrium solubility compared with pure rutin. 32 Paczkowska et al obtained a rutin-β-cyclodextrin complex by cogrinding, and the solubility of rutin and the rutin-β-cyclodextrin complex was studied. The rutin-β-cyclodextrin complex showed higher solubility in different buffers.…”