Tailor-made electrically-responsive poly(acrylamide)-graft-pullulan copolymer based transdermal drug delivery systems: Synthesis, characterization, in-vitro and ex-vivo evaluation

An electrically-responsive poly (acrylamide)-graft-pullulan (PAAm-g-PLN) copolymer was synthesized in an inert atmosphere using nitrogen gas and was characterized by H-1 NMR spectroscopy, FTIR spectroscopy, elemental analysis and thermal analysis. Further, we have developed electrically-responsive transdermal delivery systems (ETDS) utilizing PAAm-g-PLN hydrogel as reservoir for drug and pullulan-poly (vinyl alcohol) films as rate controlling membrane (RCM) for delivery of rivastigmine tartarate through skin. Under no electric stimulation, the drug diffusion through ETDS was small and when electric stimulation was applied, the diffusion rate enhanced to 1.68 folds. The drug permeation tends to get reduced as glutaraldehyde (GA) concentration was increased. On the other hand, the permeation rate was observed to augment under the influence of electric stimulus when increased from 2 to 8 mA. The drug permeation with on-off electric stimulus mode showed a quicker permeation of drug when electric stimulus was in 'on' mode and it got decreased when electric stimulus turned to 'off' mode. The skin histopathology evaluation suggested a reversible alteration in skin structure when electric stimulation was applied. Thus, the novel PAAm-g-PLN electrically-responsive copolymer is an efficient biomaterial for transdermal delivery of drugs actuated by an electric stimulus.