Evaluating the mucoprotective effects of glycyrrhizic acid-loaded polymeric nanoparticles in a murine model of 5-fluorouracil-induced intestinal mucositis via suppression of inflammatory mediators and oxidative stress

Abstract

Objectives: 5-Flourouracil (5-FU), a chemotherapeutic drug, is linked with severe deteriorating effects on intestine leading to mucositis. Further, Glycyrrhizic acid is a renown herbal medicine with combined mucoprotective, antioxidant and anti-in ammatory actions, however associated with pharmacokinetics limitations. Owing to its remarkable therapeutic action in in ammatory bowel disease inside the polymeric nanocarriers, we have tried to explore its activity against 5-FU led intestinal mucositis. Polymeric nanocarriers proved to be e cient drug delivery vehicles for long-term remedy against in ammatory diseases, however, yet not explored for 5-FU induced mucositis. Therefore, the study aimed to produce Glycyrrhizic acid loaded poly lactic-co-glycolic acid (GA-PLGA) nanoparticles to evaluate its protective and therapeutic effects on intestinal mucosa against 5-FU mediated mucositis.Methods: For the said purpose, GA-PLGA nanoparticles were prepared using modi ed double emulsion method, physicochemically characterized and tested for invitro drug release. Thereafter, mucositis was induced by 5-FU (50 mg/kg; IP) administration to the mice for the rst three days (day 0, 1, 2) and orally treated with GA-PLGA nanoparticles till seventh day (day 0-6).Results: GA-PLGA nanoparticles signi cantly reduced mucositis severity as manifested through recovered body weight, diarrhea score, distress, and anorexia. Further, 5-FU induced intestinal histopathological damage, altered villi-crypt length, low goblet cell count, elevated pro-in ammatory mediators and suppressed antioxidant enzymes were reversed by GA-PLGA nanoparticles' sustained release therapeutic action.Conclusion: Morphological, behavioral, histological, and biochemical results suggested that GA-PLGA nanoparticles found to be e cient, biocompatible, targeted, sustained release drug delivery nano-vehicle for enhanced mucoprotective, anti-in ammatory and antioxidant effects in ameliorating 5-FU intestine mucositis. IntroductionIntestinal mucositis is clinically characterized through severe abdominal pain, nausea, vomiting, bloating, diarrhea, and abdominal cramps because of underlying mucosal in ammation and loss of epithelial lining that ends up in mucosal ulceration of the gastrointestinal tract (Blijlevens et al. 2000;Logan et al. 2009). It is one of the inevitable side effects associated with cancer chemotherapy (van Vliet et al. 2010), affecting almost 40% of the patients receiving standard doses and about 80-100% of the patients who received higher doses of chemotherapy (Keefe et al. 1997;Lalla et al. 2014). Chemotherapeutic agents, in general, interfere with rapidly dividing cells, therefore, fast proliferating mucosal cells are more prone to these agents (Duncan and Grant 2003). Intestinal mucositis halt chemotherapeutic regimen and alter the dosing schedule, thereby contributing towards higher mortality in the cancer patients (Naidu et al. 2004).Recently, research paradigm concentrates on the resolution of intestinal injury caused by chemotherapeutic agents. 5...

Synergistic Effects of Licorice Root and Walnut Leaf Extracts on Gastrointestinal Candidiasis, Inflammation and Gut Microbiota Composition in Mice

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