Nanotransethosomal co-drug delivery system of diclofenac sodium and rosmarinic acid against rheumatoid arthritis: design, formulation, characterisation and pre-clinical studies

Rosmarinic acid, an ester between caffeic acid and 3,4-dihydroxyphenyllactic acid, is distributed in broad distribution throughout plants within the Boraginaceae family and Nepetoideae subfamily of Lamiaceae. It has been identified with its multifaceted biological and pharmacological activities and thus has been the subject of significant interest for therapeutic application. Diclofenac sodium is a widely used NSAID for pain relief and inflammation control. Here, a transethosomal delivery form of rosmarinic acid & diclofenac sodium (RD-TE) was prepared and formulated into a gel for local application. Optimisation was performed utilising the Box-Behnken design, determining the effect of three independent variables Phospholipid 90 G, sodium cholate, and ethanol on vesicle size, polydispersity index (PDI), and entrapment efficiency. The optimised formulation (RD-TE-Opt) had a vesicle size of 110.9 nm, PDI of 0.37, zeta potential of -20.76 mV, % entrapment efficiency of romarinic acid and diclofenac sodium was found to be 82.44 and 81.23% respectively. In vivo evaluation using an arthritic rat model demonstrated a significant reduction in paw volume, from 3.65 ± 0.03 to 3.42 ± 0.04, along with an RBC count of 8.23 ± 0.03 in the group treated with RD-TE-OptG. Radiographic analysis confirmed the therapeutic efficacy of the formulation. RD-TE gel shows potential as a topical arthritis treatment.