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

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/cm 2 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.

Recent advances in ultrasound-based transdermal drug delivery

“…Research by Pamornpathomkul et al 44 examined the effects of combining low-frequency SP with microneedles in the in vitro transdermal delivery of fluorescein isothiocyanate-dextrans. By using confocal laser scanning microscopy, they determined that the magnitude of fluorescence was greatest when the two transdermal drug delivery techniques were combined, when compared with using each method individually.…”

Transdermal Drug Delivery Systems: A Focused Review of the Physical Methods of Permeation Enhancement

“…The in vitro permeation experiment demonstrated that the extent of permeation was greater for the combination of microneedles and sonophoresis than for each method alone. 98 Manikkath et al aimed to evaluate the individual and collective impacts of peptide dendrimers and low-frequency ultrasound on the permeability of transdermally administered ketoprofen. The results of the study indicated that combining peptide dendrimer treatment with ultrasound application exhibited enhancement ratios of up to 1369.15.…”

Recent advances on biomechanical motion-driven triboelectric nanogenerators for drug delivery

“…The microneedle system provides some advantages: i) site-specific delivery with exact penetration depth ii) painless drug delivery with a high flow rate of drug iii) minimal skin damage with the flexibility of uses at any time. To ensure a high output delivery Pamornpathomkul et al [99] tested the combined effects of low-frequency SP with microneedles in vitro TDD of fluorescein isothiocyanate dextrans (FSD). The result showed the greatest delivery at combined technique rather than individual method.…”