Kinetics of skin resealing after insertion of microneedles in human subjects

Abstract

Over the past decade, microneedles have been shown to dramatically increase skin permeability to a broad range of compounds by creating reversible microchannels in the skin. However, in order to achieve sustained transdermal drug delivery, the extent and duration of skin‘s increased permeability needs to be determined. In this study, we used electrical impedance spectroscopy to perform the first experiments in human subjects to analyze the resealing of skin‘s barrier properties after insertion of microneedles. Microneedles having a range of geometries were studied in conjunction with the effect of occlusion to test the hypothesis that increasing microneedle length, number, and cross-sectional area together with occlusion leads to an increase in skin resealing time that can exceed one day. Results indicated that in the absence of occlusion, all microneedle treated sites recovered barrier properties within 2 h, while occluded sites resealed more slowly, with resealing windows ranging from 3-40 h depending on microneedle geometry. Upon subsequent removal of occlusion, the skin barrier resealed rapidly. Longer microneedles, increased number of needles, and larger cross-sectional area demonstrated slower resealing kinetics indicating that microneedle geometry played a significant role in the barrier resealing process. Overall, this study showed that pre-treatment of skin with microneedles before applying an occlusive transdermal patch can increase skin permeability for more than one day, but nonetheless allow skin to reseal rapidly after patch removal.

Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation

“…The electrical impedance technique, Figure 7, exploits the SC's electrical insulating properties to provide information on skin barrier function and confirm if MNs have successfully compromised the SC [48]. A strong inverse correlation between skin permeability and skin electrical impedance has been demonstrated [58,60]. Yan et al [6] recognised a linear relationship between acyclovir flux and the inverse of skin electrical resistance.…”

“…Assessing MN piercing of the skin, and the corresponding insertion force required to cause successful penetration, has been investigated by a number of groups through the use of electrical impedance methods [41,44,48,58,59]. In this context, impedance is the phase dependant resistance of the skin to the flow of alternating current.…”

Enhancement of skin permeation of vitamin C using vibrating microneedles

“…[30] The kinetics of pore resealing after microneedle insertion have been studied in human subjects by electrical impedance measurements, which showed that pores formed by microneedles recovered their barrier properties within 2 h when the skin was not occluded, but took 3 to 40 h to recover when the skin was occluded, depending on the geometry of the microneedles. [31,32] The kinetics of pore resealing were also studied in hairless rats using TEWL and tissue staining, and showed similar timeframes for pore resealing. [33] For the present vibrating microneedles, 5 min of application time was optimal for the transdermal delivery of vitamin C. Skin irritation scores for vitamin C gel were zero, which indicated the safety and acceptability of vibrating microneedles for transdermal administration of vitamin C gel.…”

Microneedle Manufacture: Assessing Hazards and Control Measures

“…In the case of manufacturing laboratories, the assumption is that any application to human skin occurs as a result of accident and that there will therefore be no prior treatment. It has been shown that the potential for bacterial infection arising from microneedle applications is considerably lower when compared with conventional injection systems [9,28], and, under non-occlusive conditions, the microchannels would be expected to heal within 2 h of the initial puncture [29]. The situation becomes more ambiguous where there is a failure in the dissolution or removal of a dissolvable/swellable microneedle such that partially dissolved needle fragments continue to bridge the skin barrier [1].…”