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Effectiveness of budesonide-succinate-dextran conjugate as a novel prodrug of budesonide against acetic acid-induced colitis in rats

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background

Anti-inflammatory drugs with high potency and low systemic adverse effects, such as budesonide, are drugs of choice for the treatment of ulcerative colitis (UC). Budesonide controlled-release formulations are now being used to induce and maintain clinical remission of Crohn's disease. Budesonide-dextran conjugates were synthesized as novel prodrugs of budesonide for oral controlled delivery of the major part of the drug to the colon without needing to coat the pellets of the drug. The aim of this study was to evaluate the in vivo efficacy of this conjugate against acetic acid-induced colitis in rats.

Materials and methods

Experimental UC was induced by rectal instillation of 4% solution of acetic acid to rats. After induction of colitis, rats were treated with vehicle (dextran solution), mesalasine (120 mg/kg), budesonide suspension (300 μg/kg) and BSD-70 (equivalent to 300 μg/kg of budesonide), prednisolon (4 mg/kg), hydrocortisone acetate enema (20 mg/kg), and 5-ASA enema (Asacol®) (400 mg/kg) for 5 days and then colon macroscopic and microscopic sections were examined for inflammatory response.

Results

Vehicle-treated rats presented bloody diarrhoea and gross lesions. The effective formulations for attenuating the damage were BSD-70, oral prednisolon and hydrocortisone acetate enema. Rats treated with BSD-70 showed huge improvement in macroscopic and histological scores of colitis compared to the negative control group and mesalasine and budesonide suspension.

Conclusion

Data indicated that budesonide-dextran conjugate is effective in improving signs of inflammation in experimental model of colitis through selective delivery of the drug to the inflamed area.

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Acknowledgments

This project was supported by a research grant from the Vice Chancellery of Research of the Isfahan University of Medical Sciences. The authors wish to thank AstraZeneca Company for providing budesonide samples.

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy and Isfahan Pharmaceutical Sciences Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran

    Jaleh Varshosaz, Jaber Emami, Naser Tavakoli & Fatemeh Ahmadi

  2. Department of Medicinal Chemistry, Faculty of Pharmacy and Isfahan Pharmaceutical Sciences Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran

    Afshin Fassihi

  3. Department of Pharmacology, Faculty of Pharmacy and Isfahan Pharmaceutical Sciences Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran

    Mohsen Minaiyan

  4. Department of Pathology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Parvin Mahzouni

  5. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Farid Dorkoosh

Authors
  1. Jaleh Varshosaz
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  2. Jaber Emami
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  3. Afshin Fassihi
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  4. Naser Tavakoli
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  5. Mohsen Minaiyan
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  6. Fatemeh Ahmadi
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  7. Parvin Mahzouni
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  8. Farid Dorkoosh
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Correspondence to Jaleh Varshosaz.

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Varshosaz, J., Emami, J., Fassihi, A. et al. Effectiveness of budesonide-succinate-dextran conjugate as a novel prodrug of budesonide against acetic acid-induced colitis in rats. Int J Colorectal Dis 25, 1159–1165 (2010). https://doi.org/10.1007/s00384-010-1026-2

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  • DOI: https://doi.org/10.1007/s00384-010-1026-2

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