Artificia Therio-Responsive Membrane Able to Control On-Off Switching Drug Release through Nude Mice Skin without Interference from Skin-Penetrating Enhancers

Abstract

The influence of skin-penetrating enhancers such as Azone, ethanol and propylene glycol (PG) on the on-off switching penetration behavior of salbutamol sulfate through the thermo-responsive cholesteryl oleoyl carbonate (COC)-embedded membrane with or without application to the excised nude mice skin was examined. Without the nude mice skin, gel formulations without any enhancer and with Azone showed higher drug penetration across the COC-embedded membrane than those with ethanol and propylene glycol (PG). Moreover, the on-off switching function of COC-embedded membrane still existed. These results indicate that Azone did not alter the thermo-responsive property of COC-embedded membrane. A lower penetration behavior associated with ethanol or PG was probably due to the increased solubility of salbutamol sulfate in each gel formulation and improved drug-carbopol gel interaction. The application of COC-embedded membrane to excised nude mice skin resulted in a similar on-off switching penetration behavior to the gel, but the penetration was significantly weakened compared to the gel formulation that only penetrated through the COC-embedded membrane. However, passage of salbutamol sulfate across the COC-embedded membrane applied to the excised nude mice skin was severely restricted when an enhancer was absent from the gel. Obviously, the excised skin was the predominant barrier to drug penetration. The present study suggests that skin-penetrating enhancer does not alter the structure of the COC embedded in membrane to change the thermo-responsive on-off switching penetration behavior of salbutamol sulfate from gel formulas through COC-embedded membrane.