Dendrimer-coupled sonophoresis-mediated transdermal drug-delivery system for diclofenac

Abstract

Bin Huang,1 Wei-Jiang Dong,2 Gao-Yi Yang,3 Wei Wang,1 Cong-Hua Ji,1 Fei-Ni Zhou4 1Department of Ultrasound, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 2Department of Ultrasonography, Tongxiang Chinese Medicine Hospital, Jiaxing, 3Department of Ultrasound, Hangzhou Red Cross Hospital, 4Department of Medical Records and Statistics, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China Abstract: The purpose of the present study was to develop a novel transdermal drug-delivery system comprising a polyamidoamine dendrimer coupled with sonophoresis to enhance the permeation of diclofenac (DF) through the skin. The novel transdermal drug-delivery system was developed by using a statistical Plackett–Burman design. Hairless male Wistar rat skin was used for the DF-permeation study. Coupling media concentration, ultrasound-application time, duty cycle, distance from probe to skin, and a third-generation polyamidoamine-dendrimer concentration were selected as independent variables, while in vitro drug release was selected as a dependent variable. Independent variables were found to be statistically significant (P<0.05). DF gel without dendrimer and ultrasound treatment to skin (passive delivery, run 13) showed 56.69 µg/cm2 cumulative drug permeated through the skin, while the DF-dendrimer gel without sonophoresis treatment (run 14) showed 257.3 µg/cm2 cumulative drug permeated through the skin after 24 hours. However, when the same gel was applied to sonophoresis-treated skin, drastic permeation enhancement was observed. In the case of run 3, the cumulative drug that permeated through the skin was 935.21 µg/cm2. It was concluded that dendrimer-coupled sonophoresis-mediated transdermal drug delivery system has the potential to enhance the permeation of DF through the skin. Keywords: sonophoresis, ultrasound, polyamidoamine, permeation enhancers, stratum corneum