Transdermal drug administration presents several advantages and it is therefore favorable\nas an alternative drug delivery route. However, transdermal delivery of biopharmaceutical drugs is\nmade difficult by the skin barrier. Microneedle application and iontophoresis are strategies which\ncan be used to overcome this barrier. Therefore, recombinant human growth hormone (rhGH)\nwas used as a model macromolecular drug and was transdermally delivered using microneedle\napplication and iontophoresis. Methylene blue staining, stereomicroscopy and scanning electron\nmicroscope (SEM) imaging were used to characterize the microchannels produced. To optimize the\niontophoresis protocol, the effects of molecular charge and current density on transdermal delivery\nwere evaluated in an in vitro permeation study using excised rat skin tissues. Using the optimized\niontophoresis protocol, the combination effects of iontophoretic delivery via microchannels were\nevaluated in three different experimental designs. The flux obtained with anodal iontophoresis\nin citrate buffer was approximately 10-fold higher that that with cathodal iontophoresis in\nphosphate buffered saline (PBS). Flux also increased with current density in anodal iontophoresis.\nThe combination of iontophoresis and microneedle application produced higher flux than single\napplication. These results suggest that anodal iontophoresis with higher current density enhances\nthe permeation of macromolecules through microchannels created by microneedles. In conclusion,\nthe combination of iontophoresis and microneedles is a potential strategy for the enhancement of\ntransdermal delivery of macromolecular drugs.
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