Study on preparation of sinomenine hydrochloride transfersomes and their therapeutic effects on rheumatoid arthritis in rats / 中草药

ABSTRACT

Objective To optimize the formulation of sinomenine hydrochloride transfersomes (SHTs) and to verify their therapeutic effects on rheumatoid arthritis in rats. Methods SHTs were prepared by ethanol injection method. Their formulation was optimized by an orthogonal test, which was based on the elasticity of transfersomes. Elasticity of transfersomes was measured by constant pressure extrusion method and entrapment efficiency was measured by HPLC combined with centrifugation ultrafiltration. The model of rheumatoid arthritis was established by subcutaneous injection of type II collagen into Wistar rats' tail. The therapeutic effects of the preparation on rheumatoid arthritis in rats were evaluated based on ankle joint score, swelling degree, level of TNF-α and IL-1β in serum as well as histological changes including inflammatory cell infiltration, pannus formation, cartilage destruction, and bone erosion. Results The optimized formulation was as follows: egg phospholipid 300 mg, cholesterol 30 mg, sinomenine hydrochloride 100 mg, sodium deoxycholate 60 mg, vitamin E 5 mg, phosphate buffered saline (pH 8.0) 23 mL, and absolute ethyl alcohol 2 mL. The optimized transfersomes had an average size of (83.31 ± 0.08) nm, Zeta potential of (-32.57 ± 3.27) mV, deformability index of 38.69 ± 1.66, drug content of (2.96 ± 0.27) mg/mL, and entrapment efficiency of (39.82 ± 0.97) %. The results of pharmacodynamical test revealed that the preparation could significantly reduce joint swelling caused by rheumatoid arthritis (P < 0.01) and lower TNF-α and IL-1β level in serum (P < 0.01), effectively alleviate inflammatory response and improve histological changes of ankle joint. Conclusion The preparation process for the transfersomes is feasible and their quality can be controlled. The optimized SHTs are effective for treatment of rheumatoid arthritis in rats.