Low frequency ultrasound and PAMAM dendrimer facilitated transdermal delivery of ketoprofen

The aim of the present study was to investigate the combined effect of PAMAM dendrimers and low-frequency ultrasound on the transdermal delivery of ketoprofen. Ketoprofen was subjected to in vitro and in vivo permeation studies involving passive diffusion (+/-PAMAM dendrimers (amine terminated; G1 to G4)) and sonophoretic permeation (+/-dendrimer application) across mouse skin. The dendrimer was applied to skin either along with the drug (simultaneous application) or prior to treatment with drug (pretreatment). Skin permeation studies for prepared drug-dendrimer complex were also performed. Both PAMAM dendrimers and sonophoresis used individually increased the transdermal permeation of the drug, but the combination of these two enhancement techniques showed a profound increase in the skin permeation of drug. Pretreatment mode of dendrimer application achieved higher drug permeation, both in presence and absence of ultrasound. Complexation of ketoprofen with G4 dendrimer resulted in lesser skin permeation of drug in the absence of ultrasound, and higher skin permeation in the presence of ultrasound. The combination of PAMAM dendrimer application along with ultrasound produced plasma drug levels similar to oral administration of ketoprofen. This study demonstrates the potential of combining PAMAM dendrimers with sonophoresis in achieving higher skin delivery of bioactive molecules.