ADVANCES IN AMELIORATING RHEUMATOID ARTHRITIS BY ANDROGRAPHOLIDE ETHOSOME-BASED GEL: PHARMACOKINETIC AND ACTIVITY STUDY IN RATS

Abstract

Objective: Andrographolide is the primary active constituent that was isolated from Andrographis paniculata and has been adopted to treat rheumatoid arthritis. Several studies revealed that it has poor oral bioavailability and skin penetration, which can be solved through the transdermal delivery of ethosomes. Therefore, this study aims to determine the pharmacokinetic profiles, relative bioavailability, and efficacy of andrographolide in the form of transdermal ethosomal gel in rheumatoid arthritis (RA) animal models. Methods: Andrographolide was processed into ethosomes using the thin layer hydration-sonication technique. Its physical properties were then characterized, including particle size, polydispersity index, zeta potential, and entrapment efficiency, before it was incorporated into a gel dosage form. An in vivo study was also carried out on male Sprague Dawley rats. Subsequently, two gels, namely ethosomal and non-ethosomal, as well as an oral solution were prepared for the pharmacokinetic study. For the anti-rheumatic activity, thirty-six male rats were divided into three controls as well as three treatment groups, which were treated with 25, 50, and 100 mg/kg of andrographolide. During the induction and post-treatment phases, clinical manifestations of arthritis were thoroughly monitored. Results: The andrographolide ethosomes were successfully prepared with particle sizes of 76.35±0.74 nm and entrapment efficiency of 97.87±0.23%. Based on the pharmacokinetic studies, the Cmax obtained for ethosomal and non-ethosomal gel, as well as oral suspension, were 53.07±4.73, 27.34±1.48, and 11.72±0.74 μg/ml with AUC0-∞ of 152.10±16.53, 77.15±12.28, and 23.20±3.46 μg. h/ml, respectively. Furthermore, the relative bioavailability recorded for the preparations was 655.60%. Anti-rheumatic activity investigations revealed that the 50 and 100 mg/kg ethosomal gels reduced oedema volume closely with 0.135 mg methotrexate subcutaneously. Conclusion: The ethosomal gel enhanced Cmax, AUC0-∞, and the relative bioavailability of andrographolide. Furthermore, it reduced oedema volume, ankle joint diameter, and arthritic scores in RA rats.