To improve the transdermal bioavailability and safety of alendronate (ALN), a nitrogencontaining\nbisphosphonate, we developed self-dissolving microneedle arrays (MNs), in which ALN\nis loaded only at the tip portion of micron-scale needles by a dip-coating method (ALN(TIP)ââ?¬â??MN).\nWe observed micron-scale pores in rat skin just after application of ALN(TIP)ââ?¬â??MN, indicating that\ntransdermal pathways for ALN were created by MN. ALN was rapidly released from the tip of MNs\nas observed in an in vitro release study. The tip portions of MNs completely dissolved in the rat\nskin within 5 min after application in vivo. After application of ALN(TIP)ââ?¬â??MN in mice, the plasma\nconcentration of ALN rapidly increased, and the bioavailability of ALN was approximately 96%.\nIn addition, the decrease in growth plate was effectively suppressed by this efficient delivery of\nALN in a rat model of osteoporosis. Furthermore, no skin irritation was observed after application\nof ALN(TIP)ââ?¬â??MN and subcutaneous injection of ALN, while mild skin irritation was induced by\nwhole-ALN-loaded MN (ALNââ?¬â??MN)ââ?¬â?in which ALN is contained in the whole of the micron-scale\nneedles fabricated from hyaluronic acidââ?¬â?and intradermal injection of ALN. These findings indicate\nthat ALN(TIP)ââ?¬â??MN is a promising transdermal formulation for the treatment of osteoporosis without\nskin irritation.
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