This study characterizes skin perforation by commercially available microneedle rollers and evaluates the efficacy of transdermal delivery of insulin to diabetic rats. Three different needle lengths, 250, 500 and 1000 microm, were used in this work. Creation and resealing of the skin holes that were produced by the needles were observed by Evan's blue (EB) staining and transepidermal water loss (TEWL) measurements. EB clearly showed that microchannels were formed in the skin and that the pores created by the longest microneedle (1000 microm) persisted no longer than 8h, while the hypodermic injury was still observed 24h later. TEWL significantly increased after the application of the needles and then decreased with time, which explains the recovery of skin barrier function and agrees well with EB results. The extent of permeation was demonstrated by insulin delivery in vivo. The rapid reduction of blood glucose levels in 1h was caused by the increased permeability of the skin to insulin after applying microneedle rollers. The reduced decrease after 1h is closely associated with hole recovery. In conclusion, microneedle rollers with 500-microm or shorter lengths are safe and useful in transdermal delivery of insulin in vivo.
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