Development of voltage gated transdermal drug delivery platform to impose synergistic enhancement in skin permeation using electroporation and gold nanoparticle

摘要

Owing to poor skin permeability, the transdermal (TRD) drug delivery at the required therapeutic rate still remains an arduous task. In the present investigation, a novel TRD enhancement strategy was introduced using the synergistic effect of gold nanoparticle (GNP) and skin electroporation. Diclofenac sodium (DS) was selected as a model drug. An electro-sensitive patch was constructed using skin adhesive matrix, polyvinyl alcohol/poly(dimethyl siloxane)-g-polyacrylate. GNP/ carbon nanotube nanocomposite (GNP-CNT) was incorporated into the matrix with GNP and CNT to enhance skin permeability and electrical conductivity, respectively. Varying the concentration of GNP-CNT, alters the thermomechanical properties, water vapor permeability (WVP), drug encapsulation efficiency (DEE) and drug release profile, building a possibility to fine-tune the properties of the device. The membrane constructed with 1.5% GNP-CNT displayed the highest DEE and thermomechanical properties. The TRD DS release study was performed in rat skin at different GNP-CNT contents and variable conditions of applied voltage. Incorporating GNP-CNT enhanced the DS permeation profile with the best performance exhibited by device containing 1.5% nanofillers at an applied bias of 10.0 V. Electroporation in conjugation with GNP remarkably destroys the stratum comeum (SC) barrier by disparate mechanisms involving the breakdown of multilamellar lipid system, generation of new aqueous pathway and thermal effect. Furthermore, the dramatic disruption of lipid barriers generated by applied voltage was efficiently stabilized by GNP in addition to the transient and reversible openings created by them. Finally the safety of the device was confirmed by cell viability assay and environmental stability test. The developed skin permeation approach may open new avenues in TRD drug delivery.