Nanosized ethosomes bearing ketoprofen for improved transdermal delivery

Abstract

The potential of ethosomes for delivering ketoprofen via skin was evaluated. The ethosomes were prepared, optimized and characterized. Vesicular shape, size and entrapment efficiency were determined by transmission electron microscopy, dynamic light scattering and minicolumn centrifugation technique, respectively. Vesicle sizes varied from 120.3±6.1 to 410.2±21.8 nm depending on the concentrations of soya phosphatidyl choline (SPC) and ethanol. Entrapment efficiency increased with concentrations of SPC and ethanol. The formulations exhibited entrapment efficiencies of 42-78%. In vitro release through cellophane membrane showed sustained release of drug from ethosomal formulations in contrast to hydroalcoholic drug solution (HA), which released most of the drug within 2-3 h. In vitro drug permeation across human skin revealed improved drug permeation and higher transdermal flux with ethosomal formulations compared to hydroethanolic drug solution. Kinetics of in vitro skin permeation showed zero order drug release from formulations. Based on in vitro transdermal flux, the estimated steady state in vivo plasma concentration from ethosomes attained therapeutic drug levels whereas hydroalcoholic drug solution exhibited sub therapeutic drug concentration with a patch size of 50 cm(2). Skin permeation of ethosomal formulations assessed by confocal microscopy revealed enhanced permeation of Rhodamine 123 loaded formulation in comparison to the hydroalcoholic solution.

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“…This is also in accordance with previous findings of Chourasia et al, 2011. [19] HA drug solution released most of the drug within 2-4 h. Cumulative amount of drug permeated per unit area versus time graph was plotted and transdermal flux (J) was calculated from the slope of linear portion [ Figure 2a]. On the analysis of transdermal flux of the same formulations, it was found that results followed the similar pattern as that of cumulative percent drug release [ Figure 2b] which varied from 66.69163.5 µg/cm 2 /h (conventional gel) to 163.5 µg/cm 2 /h (GEL F12).…”

“…This observation supports the findings, of [18,19] which state that higher concentration of ethanol is responsible for decrease in the size of vesicle as it furnish a surface negative net charge to the vesicular systems by altering some surface characteristics.…”

“…Ethanol provides the vesicles soft flexible characterstics which allow then to permeate more readily into deeper layers of skin. This is also in accordance with previous findings of Chourasia et al, 2011. [19] HA drug solution released most of the drug within 2-4 h. Cumulative amount of drug permeated per unit area versus time graph was plotted and transdermal flux (J) was calculated from the slope of linear portion [ Figure 2a].…”

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“…Chan et al [65] developed nanosized ethosomes bearing ketoprofen for improved transdermal delivery. Ethosomal vesicles were prepared by the method reported elsewhere with some modifications.…”

Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations

“…6,92 A preclinical study testing the efficacy of ketoprofen in ethosomes for transdermal drug delivery was recently published. 93 Improved drug permeation across human skin and higher transdermal flux with ethosomal formulations compared to hydroethanolic drug solution was revealed in vitro. Based on transdermal flux, the estimated steady state in vivo plasma concentration from ethosomes attained therapeutic drug levels, whereas the hydroethanolic drug solution exhibited subtherapeutic drug concentrations with a patch size of 50 cm 2 .…”