Antiarthritic and Chondroprotective Activity of Lakshadi Guggul in Novel Alginate-Enclosed Chitosan Calcium Phosphate Nanocarriers

Abstract

Aim: This study aimed to evaluate the antiarthritic and chondroprotective potentials of Lakshadi Guggul (LG) and Cissus quadrangularis encapsulated in novel alginate-enclosed chitosan–calcium phosphate nanocarriers (NCs) both in vitro in primary human chondrocytes and in vivo in mice with collagen-induced arthritis. Materials & methods: Chondrocytes exposed to IL-1β and osteoarthritis chondrocytes grown in an ex vivo inflammation-based coculture were incubated with different concentrations of herbals, and cell modulatory activities were determined. For in vivo studies, herbals and their encapsulated nanoformulations were administered orally to DBA/1 mice with collagen-induced arthritis. Results:C. quadrangularis and LG showed enhanced chondroprotective and proliferative activity in IL-1β-exposed primary chondrocytes, with LG showing the highest therapeutic potency. LG increased viability, proliferative and mitogenic activity, and inhibited cell apoptosis and mitochondrial depolarization. In vivo studies with LG and alginate-enclosed chitosan–calcium phosphate LG NCs revealed cartilage regenerative activity in those administered with the nanoformulation. The NCs were nontoxic to mice, reduced joint swelling and paw volume, and inhibited gene expression of MMPs and cytokines. Conclusion: The promising results from this study reveal, for the first time, the novel polymeric NC encapsulating LG as a potential therapeutic for rheumatic diseases.

Keywords::

• alginate
• anti-inflammatory
• antiarthritic
• chitosan
• Cissus quadrangularis
• collagen-induced arthritis
• Lakshadi Guggul
• nanocarrier
• oral delivery
• osteoarthritis

Financial & competing interests disclosure

The authors would like to thank the Australia–India Strategic Research Fund (AISRF) and National Health and Medical Research Council (NHMRC) for financial support. A patent application has been filed based on some data presented in this article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors would like to thank N Branson for his assistance with animal work and for his technical support and guidance with the animal experimental procedures. The authors also thank the upper animal house staff, in particular T Thorpe, A Cooper and B Newell for providing help in handling the animals.

Additional information

Funding

The authors would like to thank the Australia–India Strategic Research Fund (AISRF) and National Health and Medical Research Council (NHMRC) for financial support. A patent application has been filed based on some data presented in this article. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.