Recovery Rate of Rat Skin Micropores Made by Dissolving Microneedles

The physiological recovery rate of skin was studied using dissolving microneedles (DMs) made of chondroitin sulfate. Chips of two kinds were prepared having conical DMs as an array: (1) a 300 DM array chip having a sharp tip with mean diameter of 4.7 ± 0.2 μm, and a (2) 225 DM array chip having a less-sharp tip with mean diameter of 15.3 ± 0.3 μm. Under anesthesia, DMs were inserted into abdominal rat skin from which the hair had been removed. The kinetics of skin healing was studied by pathological and biochemical methods. At 5, 30, 45 min, and at 1 and 3 h after the removal of the DM array chip, the skin was stained with 0.25 % Evans blue solution before pathologic observations were performed. The skin physiology recovered to its normal state at 45 min with both DMs. Biochemical study was also performed by measuring the leaked amount of lactose dehydrogenase (LDH) activity. The maximum leaks, 199.3 ± 13.0 % (225 DMs) and 153.4 ± 23.2 % (300 DMs) appeared at 5 min. In both DMs, the micropores formed on the skin healed within 60 min. Pathological and biochemical examinations revealed that skin recovered to the pre-treatment level within 1 h. The effect of the adhesion length of the chips onto the skin on the skin’s recovery rate was studied by attaching two DMs to the rat skin for 6 h. Maximal leaks were detected at 5 min after administration, i.e., 157.8 ± 10.1 % for 300 DMs and 215.6 ± 5.4 % for 225 DMs. However, the leakage returned to the pretreatment level at 60 min. Therefore, DMs were found to be a low-invasive TDDS for drugs.