Drugs with poor oral bioavailability usually are administered by hypodermic injection, which causes pain, poor patient compliance, the need for trained personnel, and risk of infectious disease transmission. Transdermal (TD) delivery provides an excellent alternative, but the barrier of skin's outer stratum corneum (SC) prevents delivery of most drugs. Micrometer-scale microneedles (MNs) have been used to pierce animal and human cadaver skin and thereby enable TD delivery of small molecules, proteins, DNA, and vaccines for systemic action. Here, we present a clinical study of MN-enhanced delivery of a medication to humans. Naltrexone (NTX) is a potent mu-opioid receptor antagonist used to treat opiate and alcohol dependence. This hydrophilic and skin-impermeant molecule was delivered from a TD patch to healthy human subjects with and without pretreatment of the skin with MNs. Whereas delivery from a standard NTX TD patch over a 72-h period yielded undetectable drug plasma levels, pretreatment of skin with MNs achieved steady-state plasma concentrations within 2 h of patch application and were maintained for at least 48 h. The MNs and NTX patch were well tolerated with mild systemic and application site side effects. The MN arrays were painless upon administration and not damaged during skin insertion, and no MNs were broken off into the skin. This human proof-of-concept study demonstrates systemic administration of a hydrophilic medication by MN-enhanced TD delivery. These findings set the stage for future human studies of skin-impermeant medications and biopharmaceuticals for clinical applications.naltrexone ͉ stratum corneum ͉ drug delivery ͉ microfabrication

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.

Lead halide perovskites have displayed the highest solar power conversion efficiencies of 23% but the toxicity issues of these materials need to be addressed. Lead‐free perovskites have emerged as viable candidates for potential use as light harvesters to ensure clean and green photovoltaic technology. The substitution of lead by Sn, Ge, Bi, Sb, Cu and other potential candidates have reported efficiencies of up to 9%, but there is still a dire need to enhance their efficiencies and stability within the air. A comprehensive review is given on potential substitutes for lead‐free perovskites and their characteristic features like energy bandgaps and optical absorption as well as photovoltaic parameters like open‐circuit voltage (VOC), fill factor, short‐circuit current density (J SC), and the device architecture for their efficient use. Lead‐free perovskites do possess a suitable bandgap but have low efficiency. The use of additives has a significant effect on their efficiency and stability. The incorporation of cations like diethylammonium, phenylethyl ammonium, phenylethyl ammonium iodide, etc., or mixed cations at different compositions at the A‐site is reported with engineered bandgaps having significant efficiency and stability. Recent work on the advancement of lead‐free perovskites is also reviewed.

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Background Microneedles have previously been used to deliver insulin to animal models, but not in human subjects. This study tested the hypothesis that hollow microneedles can deliver insulin to modulate blood glucose levels in subjects with type 1 diabetes in a minimally invasive manner. Methods This study was carried out in two adults with type 1 diabetes and evaluated bolus delivery of lispro insulin using a hollow microneedle compared to a catheter infusion set (9 mm). The study first determined the minimum insulin delivery depth by administering insulin from microneedles inserted 1, 3.5, and 5 mm into the skin of fasting subjects and then assessed the efficacy of insulin delivery from microneedles inserted 1 mm into the skin to reduce postprandial glucose levels. Blood samples were periodically assayed for plasma free insulin and plasma glucose levels for up to 3.5 h. Results The first phase of the study indicated that microneedles inserted at the shallowest depth of 1 mm within the skin led to rapid insulin absorption and reduction in glucose levels. Bolus insulin delivery followed by consumption of a standardized meal in the second phase revealed that microneedles were effective in reducing postprandial glucose levels. Subjects reported no pain from microneedle treatments, and there were no adverse events. Conclusions This study provides the first proof of concept that hollow microneedles can effectively deliver bolus insulin to type 1 diabetes subjects in a minimally invasive manner.