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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

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Abstract

Objectives

5-Fluorouracil (5-FU), a chemotherapeutic drug, has severe deteriorating effects on the intestine, leading to mucositis. Glycyrrhizic acid is a compound derived from a common herbal plant Glycyrrhiza glabra, with mucoprotective, antioxidant and anti-inflammatory actions, however, associated with poor pharmacokinetics. Owing to the remarkable therapeutic action of glycyrrhizic acid-loaded polymeric nanocarriers in inflammatory bowel disease, we explored their activity against 5-FU-induced intestinal mucositis in mice. Polymeric nanocarriers have proven to be efficient drug delivery vehicles for the long-term treatment of inflammatory diseases, but have not yet been explored for 5-FU-induced mucositis. Therefore, this study aimed to produce glycyrrhizic acid-loaded polylactic-co-glycolic acid (GA-PLGA) nanoparticles to evaluate their protective and therapeutic effects in a 5-FU-induced mucositis model.

Methods

GA-PLGA nanoparticles were prepared using a modified double emulsion method, physicochemically characterized, and tested for in vitro drug release. Thereafter, mucositis was induced by 5-FU (50 mg/kg; IP) administration to the mice for the first 3 days (day 0, 1, 2), and mice were treated orally with GA-PLGA nanoparticles for 7 days (day 0–6).

Results

GA-PLGA nanoparticles significantly reduced mucositis severity measured by body weight, diarrhea score, distress, and anorexia. Further, 5-FU induced intestinal histopathological damage, altered villi-crypt length, reduced goblet cell count, elevated pro-inflammatory mediators, and suppressed antioxidant enzymes, all of which were reversed by GA-PLGA nanoparticles.

Conclusion

Morphological, behavioral, histological, and biochemical results suggested that GA-PLGA nanoparticles were efficient, biocompatible, targeted, and sustained release drug delivery nano-vehicle for enhanced mucoprotective, anti-inflammatory, and antioxidant effects in 5-FU-induced intestinal mucositis.

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Data availability

Manuscirpt has no associate data. Raw data will be available on a suitable request.

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Acknowledgements

We have acknowledged Prof. Benno Weigmann, University of Erlangen-Nürnberg, Germany, for his expert advice in the experiments.

Funding

The manuscript has been funded under HEC NRPU project No. 9272/Federal/NRPU/R&D/HEC/2017.

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Authors and Affiliations

  1. Department of Pharmacy, Quaid-I-Azam University, Islamabad, 45320, Pakistan

    Mahira Zeeshan, Ayesha Atiq, Qurat Ul Ain, Jawad Ali, Salman Khan & Hussain Ali

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  1. Mahira Zeeshan
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  2. Ayesha Atiq
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  3. Qurat Ul Ain
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  4. Jawad Ali
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  5. Salman Khan
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  6. Hussain Ali
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Correspondence to Hussain Ali.

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Authors declared no conflict of interests.

Ethics approval

All animal studies were approved and performed according to the bioethical committee protocols of Quaid-i-Azam University, Islamabad for the care and use of laboratory animals (Approval no. BES-fbs-QAU2018-75).

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Zeeshan, M., Atiq, A., Ain, Q.U. et al. 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. Inflammopharmacol 29, 1539–1553 (2021). https://doi.org/10.1007/s10787-021-00866-z

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