Enhancement of the transdermal delivery of zidovudine by pretreating the skin with two physical enhancers: microneedles and sonophoresis.

Abstract

Background: Zidovudine (AZT) has been the most widely used drug for antiretroviral therapy. In order to improve the therapy with this drug, different alternatives have been proposed, such as the transdermal administration. The use of permeation enhancers is necessary to favor the passage of this drug through the skin, due to its physicochemical properties and to the natural permeation barrier imposed by the skin.

Objectives: To evaluate the effect of two permeation enhancers, sonophoresis and microneedles, on the permeability of AZT through the skin.

Methods: Permeation studies with an AZT solution were performed using pigskin clamped in Franz-type cells. Sonophoresis was applied under different conditions (i.e., amplitude, duty cycle and application time), selected according to an experimental design, where the response variables were the increase in temperature of the skin surface and the increase in transepidermal water loss. ATR-FTIR was also used to demonstrate the effect of enhancers on membrane components.

Results: The permeability of AZT through intact skin was very poor, with a very long lag time. Pretreatment of the skin with sonophoresis increased AZT transport significantly, reducing the lag time. The maximum flux (27.52 µgcm^-2 h^-1) and the highest total amount permeated (about 624 µg/cm²) were obtained when applying sonophoresis in continuous mode, with an amplitude of 20%, and an application time of 2 min. Sonophoresis appears to have an impact on stratum corneum proteins. The use of microneedles further increased the flux (30.41 µgcm^-2 h^-1) and the total amount permeated (about 916 µg/cm²), relative to sonophoresis.

Conclusion: The results are encouraging in terms of promoting AZT transport through the skin using sonophoresis or microneedles as permeation enhancers.