Transdermal delivery of fluorescein isothiocyanate-dextrans using the combination of microneedles and low-frequency sonophoresis

摘要

Abstract This study aimed to evaluate the patient-friendly methods that are used in the delivery of hydrophilic macromolecules into deep skin layers, in particular, the combination of microneedles patch (MNs patch) and low-frequency sonophoresis (SN). The hydrophilic macromolecule drug fluorescein isothiocyanate (FITC)-dextrans (FD-4: {MW} 4.4?kDa) was used as the model drug in our experimental design. In this study, excised porcine skin was used to investigate and optimize the key parameters that determine effective MNs- and SN-facilitated FD-4 delivery. In vitro skin permeation experiments revealed that the combination of {MNs} patch with {SN} had a superior enhancing effect of skin permeation for FD-4 compared to {MNs} alone, {SN} alone or untreated skin, respectively. The optimal parameters for the combination of {MNs} and {SN} included the following: 10?N insertion force of MNs, 4?W/cm2 {SN} intensity, 6?mm radiation diameter of the {SN} probe, 2?min application time, and the continuous mode duty cycle of SN. In addition, vertical sections of skin, clearly observed under a confocal microscope, confirmed that the combination of {MNs} and {SN} enhanced permeation of FD-4 into the deep skin layers. These studies suggest that the combination of {MNs} and {SN} techniques could have great potential in the delivery of hydrophilic macromolecules into deep skin.