In vitro skin permeation of sinomenine hydrochloride PEGylated transfersomes edge activated by volatile oils / 中草药

ABSTRACT

Objective: To clarify the percutaneous absorption characteristics of sinomenine hydrochloride (SIN-HCl) PEGylated transfersomes (SHPT) edge activated by volatile oils and to compare with others carriers. Methods: Various formulations of transfersomes [The representative formulations of SHPT contained different quantity of volatile oils including SHPT-A, SHPT-B, and SHPT-C; non-PEGylated transfersomes (SHT-A and SHT-B) corresponded to SHPT-A and SHPT-B; SHDT was edge activated by sodium deoxycholate], PEGylated liposomes (SHPL), and liposomes (SHLS) were prepared by ethanol injection method. Characterization of vesicles was based on results from particle size, morphology, elasticity, and entrapment efficiency (EE) studies. Elasticity was measured by constant pressure extrusion method and EE was measured by HPLC combined with centrifugation ultrafiltration. The skin permeation test was carried out with a Franz diffusion cell fitted with excised rat skin. The effects of vesicle types (SHPT, SHDT, SHLS, and SIN-HCl aqueous solution), DSPE-PEG 2000, and volatile oil in the SHPT on percutaneous permeation of SIN-HCl were investigated. Results: The SIN-HCl transfersomes and liposomes were mainly unilamellar vesicles with roundish shape and average size of 93-118 nm, without gathering property. The entrapment efficiency was of 11%-40%. The elasticity order of vesicles was SHPT-B > SHDT ≈ SHPT-A > SHT-B > SHT-A ≈ SHPL > SHLS > SHPT-C. The steady-state drug percutaneous permeation rate [J (μg∙cm-2∙h-1)] order of different vesicles was SHT-B (19.10 ± 5.74) > SHPT-B (17.06 ± 0.34) > SHDT (15.16 ± 0.55) > SHT-A (10.96 ± 0.99) > SHPT-A (9.42 ± 1.09) > SHLS (3.90 ± 0.67) > SHPT-C (3.51 ± 0.37) > SIN-HCl aqueous solution (2.26 ± 0.94). The cumulative permeated percentages [Qe (36 h)] of SHT-B and SHPT-B were (89.79 ± 6.67)%, and (84.01 ± 6.77)%, respectively. The Qe (36 h) of SHDT, SHLS, SHPT-C and SIN-HCl aqueous solution were (73.98 ± 10.55)%, (20.29 ± 3.21)%, (15.45 ± 3.04)%, and (10.33 ± 2.91)%, respectively. The lag time of SHPT-A, SHPT-B, SHT-A, SHT-B, and SHDT (0.3-0.6 h) were significantly reduced, compared to SHLS and SIN-HCl aqueous solution (3.5-3.8 h). Conclusion: SHPT edge activated by appropriate volatile oils has good elasticity and percutaneous absorption characteristics, which is better than that of liposomes and transfersomes edge activated by sodium deoxycholate to different degrees.