Improvement of bone microarchitecture in methylprednisolone induced rat model of osteoporosis by using thiolated chitosan-based risedronate mucoadhesive film

Abstract

Objective: In this study, we investigated the potential of thiolated chitosan-based mucoadhesive film, loaded with risedronate sodium in the treatment of osteoporosis.

Significance: Risedronate sodium is a bisphosphonate derivative having very low bioavailability when administered through the oral route. Moreover, the adverse effects associated with the drug when administered through GIT necessitate an alternative and feasible route which can improve its bioavailability and therapeutic efficacy.

Methods: Thiolation of chitosan was interpreted by different analytical techniques. The mucoadhesive films were prepared by the solvent evaporation method and evaluated for drug content analysis, swelling degree, mucoadhesive parameters, and permeation characterization. For the screening of preclinical efficacy and pharmacodynamic parameters, a methylprednisolone induced osteoporotic rat model was used. The trabecular microarchitecture and biochemical markers were evaluated for determination of bone resorption.

Results: The different analytical characterization of synthesized thiolated chitosan revealed that chitosan was successfully incorporated with thiol groups. The formulation containing 2:1 ratio of thiolated chitosan and HPMC-4KM was found to have the maximum swelling degree, mucoadhesive strength with a good force of adhesion and better in vitro permeability compared to the marketed formulation. With respect to trabecular microarchitecture, the drug-loaded film formulation showed superior and promising results. Furthermore, the film formulation also improved the serum level of biomarkers better than the marketed formulation.

Conclusions: The results significantly suggest that risedronate loaded novel mucoadhesive film formulation could be a logical approach in the therapeutic intervention of osteoporosis.

Keywords:

• Thiolation
• mucoadhesive films
• osteoporosis
• risedronate sodium
• methylprednisolone
• trabecular microarchitecture

Acknowledgments

The authors would sincerely thank M. S. Ramaiah University of Applied Sciences and Gokula Education Foundation (GEF) for supporting the project. Authors gratefully acknowledge Fleming Laboratories, Hyderabad for providing gift sample of risedronate sodium. Authors are thankful to Dr. Alakkawar and Dr. Krishnaveni, Government Veterinary College, Hebbal, Bangalore in carrying out the Histopathological study and Indian Institute of Science for carrying out SEM studies. The authors wish to thank Dr. Janice Joseph, Faculty of Dental Sciences, M. S. Ramaiah University of Applied Sciences for assisting in English language editing process of the manuscript.

Disclosure statement

Authors declare no conflict of interest.