ABSTRACT
Objective To prepare dl-tetrahydropalmatine (dl-THP) ethosomes (ETS) and elucidate their transdermal absorption properties. Methods Dl-tetrahydropalmatine ethosomes (dl-THP ETS) were prepared by ethanol injection combined with pH-gradient active drug-loading method. Their physicochemical properties including elasticity, vesicle size, morphology and entrapment efficiency were characterized. Franz diffusion cells were used to investigate the ex vivo skin permeation characteristics of the formulation with liposomes (LPS) and tinctures being used as reference preparations. Results According to a preferred formulation of dl-THP ETS [dl-THP 100 mg, vitamin E 1.3 mg, soybean lecithin 1 200 mg, cholesterol 120 mg, absolute ethanol 9 mL and citrate buffered saline (pH 3.0) 21 mL, 0.1 mol/L NaOH solution suitable quantity (to adjust the pH value to 5.5) ], the obtained dl-THP ETS had an elasticity index of (20.1 ± 1.1) mL, an average size of (85.8 ± 0.9) nm with a polydispersity index of (0.082 ± 0.003) and an entrapment efficiency of (81.7 ± 3.2)%. The cumulative permeated drug quantity per unit area (Qn) of dl-THP ETS in 24 h was (2 306.4 ± 592.3) μg/cm2 with no significant difference compared with the Qn of the LPS [(2 434.2 ± 564.4) μg/cm2] (P > 0.05) and about 4 times of that of the tincture [(633.1 ± 218.0) μg/cm2] (P < 0.05). And the averages of RSD of the Qn at each time point were (28.37 ± 10.9)% and (62.83 ± 44.1)% for the ETS and LPS, respectively, indicating that the Qn fluctuation among samples of the ETS was smaller than that of the LPS (P < 0.05). Average correlation coefficients of (0.968 ± 0.033) and (0.882 ± 0.078) (P < 0.05) were obtained for the ETS and LPS respectively when their 24 h permeation curves were fitted to linear relationship, indicating the permeation of the former was closer to zero-order kinetics than that of the latter. Conclusion The dl-THP ETS have a high elasticity, a suitable size, a high entrapment efficiency, and enhanced and stable percutaneous absorption in line with zero-order kinetics.
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.