Transdermal drug delivery by in-skin electroporation using a microneedle array

Abstract

The aim of the present work was to develop a minimally invasive system for the delivery of macromolecular drugs to the deep skin tissues, so-called in-skin electroporation (IN-SKIN EP), using a microneedle (MN) electrode array. Fluorescein isothiocyanate (FITC)-dextran (FD-4: average molecular weight, 4.3 kDa) was used as the model macromolecular drug. MNs were arranged to puncture the skin barrier, the stratum corneum, and electrodes were used for EP so that a high electric field could be applied to skin tissues to promote viable skin delivery. In vitro skin permeation experiments showed that IN-SKIN EP had a much higher skin penetration-enhancing effect for FD-4 than MN alone or ON-SKIN EP (conventional EP treatment), and that higher permeation was achieved by applying a higher voltage and longer pulse width of EP. In addition, no marked skin irritation was observed by IN-SKIN EP, which was determined by the LDH leaching test. These results suggest that IN-SKIN EP can be more effectively utilized as a potential skin delivery system of macromolecular drugs than MN alone and conventional ON-SKIN EP.

A combined approach of hollow microneedles and nanocarriers for skin immunization with plasmid DNA encoding ovalbumin

“…The lipoplexes were unstable upon aggregation in the in vivo environment, especially in serum-containing environment due to the destabilization of vesicles, resulting in pDNA leakage from the carriers before reaching the target cells. 28 In the case 46 found that 48 h of exposure of the cell line dendrimers corresponded to ∼100% internalization efficiency of the tested concentrations. Moreover, the accumulation of radiolabeled dendrimers in mice was evaluated by Roberts et al, 47 and dendrimers accumulated in several organs over 48 h. These findings suggest that accumulation might occur because the expression process of dendrimer complexes did not complete within 24 h, and thus, transfection durations .24 h may be required.…”

“…27 Additionally, the combination of MN patches and EP induced a synergistic effect on macromolecule skin permeation compared with MNs alone or conventional EP. 28,29 However, until now, there has been a lack of publications on comparison of the effectivity of solid MN patches, EP patches, the combination of MN and EP patches, and hollow MNs for DNA vaccinations in skin both in vitro and in vivo.…”

“…29 Moreover, it can provide a local driving force for pOVA through the pores. 27,28 Therefore, the combination of MNs and EPs was more effective than using each device alone. These results were consistent with the findings of previous studies by Yan et al 28 and Petchsangsai et al, 29 which indicated that the combined devices significantly enhanced the skin permeation of macromolecules compared with individual methods.…”

“…27,28 Therefore, the combination of MNs and EPs was more effective than using each device alone. These results were consistent with the findings of previous studies by Yan et al 28 and Petchsangsai et al, 29 which indicated that the combined devices significantly enhanced the skin permeation of macromolecules compared with individual methods. In addition, the cumulative amount of pOVA using the hollow MNs was 2.6-fold and 2-fold higher than that of the MN patch alone and the MN+EP patch, respectively.…”

Transepidermal delivery of cosmeceuticals using radiofrequency and ultrasound: Study of the penetration of a cosmetic gel in vivo by fluorescence microscopy

“…The limiting factor for percutaneous absorption of a drug is the reservoir and penetration into the stratum corneum [1,2]. Therefore, penetration enhancement is an important task for modern dermatopharmacology [3][4][5].…”