Controlled Transdermal Iontophoresis of Insulin from Water-Soluble Polypyrrole Nanoparticles: An In Vitro Study.

The iontophoresis delivery of insulin (INS) remains a serious challenge due to the low permeability of the drug through the skin. This work aims to investigate the potential of water-soluble polypyrrole nanoparticles (WS-PPyNPs) as a drug donor matrix for controlled transdermal iontophoresis of INS. WS-PPyNPs have been prepared via a simple chemical polymerization in the presence of sodium dodecyl sulfate (SDS) as both dopant and the stabilizing agent. The synthesis of the soluble polymer was characterized using field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS), fluorescence spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy. The loading mechanism of INS onto the WS-PPyNPs is based on the fact that the drug molecules can be replaced with doped dodecyl sulfate. A two-compartment Franz-type diffusion cell was employed to study the effect of current density, formulation pH, INS concentration, and sodium chloride concentration on anodal iontophoresis (AIP) and cathodal iontophoresis (CIP) of INS across the rat skin. Both AIP and CIP delivery of INS using WS-PPyNPs were significantly increased compared to passive delivery. Furthermore, while the AIP experiment (60 min at 0.13 mA cm-2) show low cumulative drug permeation for INS (about 20.48 µg cm-2); the CIP stimulation exhibited a cumulative drug permeation of 68.29 µg cm-2. This improvement is due to the separation of positively charged WS-PPyNPs and negatively charged INS that has occurred in the presence of cathodal stimulation. The obtained results confirm the potential applicability of WS-PPyNPs as an effective approach in the development of controlled transdermal iontophoresis of INS.

Effects of chemical and physical enhancement techniques on transdermal delivery of 3-fluoroamphetamine hydrochloride.

The present study investigated the passive transdermal delivery of 3-fluoroamphetamine hydrochloride (PAL-353) and evaluated the effects of chemical and physical enhancement techniques on its permeation through human skin. In vitro drug permeation studies through dermatomed human skin were performed using Franz diffusion cells. Passive permeation of PAL-353 from propylene glycol and phosphate buffered saline as vehicles was studied. Effect of oleic acid, maltose microneedles, ablative laser, and anodal iontophoresis on its transdermal permeation was investigated. Infrared spectroscopy, scanning electron microscopy, calcein imaging, confocal laser microscopy, and histology studies were used to characterize the effects of chemical and physical treatments on skin integrity. Passive permeation of PAL-353 (propylene glycol) after 24h was found to be 1.03±0.17µg/cm2. Microneedles, oleic acid, and laser significantly increased the permeation to 7.35±4.87µg/cm2, 38.26±5.56µg/cm2, and 523.24±86.79µg/cm2 (p<0.05), respectively. A 548-fold increase in drug permeation was observed using iontophoresis as compared to its passive permeation from phosphate buffered saline (p<0.05). The characterization studies depicted disruption of the stratum corneum by microneedles and laser treatment. Overall, transdermal permeation of PAL-353 was significantly enhanced by the use of chemical and physical enhancement techniques.