Transdermal (TD) drug delivery is a more attractive technique for drug delivery compared to oral and intravenous injection. However, the permeation of drug molecules across the skin is difficult due to the presence of highly ordered lipid barrier. This study details the development of a novel TD system, which has the potential to simultaneously enhance the skin permeability and adhesion behavior. Ibuprofen (IP) was selected as model drug. The ability of gold nanoparticle (AuNP) and hydrophobic titanium nanotube (TNT) to enhance the skin permeability was explored. Additionally, β-cyclodextrin (βCD), which can exceptionally encapsulate poorly water-soluble drugs, is grafted with methacrylates to improve the skin adhesion property. Finally, Au-TNT nanocomposite was deposited onto methacrylate-grafted βCD matrix. The developed material was characterized through NMR spectroscopy, infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. The characteristics of the film, including water vapor permeability (WVP), thermomechanical properties, etc., were examined in terms of Au-TNT content. The TD delivery of IP with different concentrations of Au-TNT was evaluated via an in vitro skin permeation study through rat skin. It is revealed that the prepared TD film exhibited an improved drug-delivery performance due to the synergistic action of AuNP and hydrophobic TNT. The cumulative percent of IP delivered across the skin is extremely depending on nanofiller content, lipophilicity, and thickness of the membrane, and the device incorporated with 4.0% Au-TNT displayed the best performance. In addition, a study on storage stability was performed by storing the films for 2 months at different temperatures. The study revealed that the device possessed excellent storage stability when stored at low temperature. The developed film offers excellent WVP, drug encapsulation efficiency, thermomechanical properties, and skin adhesion behavior. Moreover, the device was cosmetically attractive, noncytotoxic, and resistant to microbial growth and hence extremely reliable for skin application. The developed skin permeation strategy may open new avenues in TD drug delivery.
