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Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis

Authors :
Hidemasa Katsumi
Yutaro Tanaka
Kaori Hitomi
Shu Liu
Ying-shu Quan
Fumio Kamiyama
Toshiyasu Sakane
Akira Yamamoto
Source :
Pharmaceutics, Vol 9, Iss 3, p 29 (2017)
Publication Year :
2017
Publisher :
MDPI AG, 2017.

Abstract

To improve the transdermal bioavailability and safety of alendronate (ALN), a nitrogen-containing bisphosphonate, we developed self-dissolving microneedle arrays (MNs), in which ALN is loaded only at the tip portion of micron-scale needles by a dip-coating method (ALN(TIP)–MN). We observed micron-scale pores in rat skin just after application of ALN(TIP)–MN, indicating that transdermal pathways for ALN were created by MN. ALN was rapidly released from the tip of MNs as observed in an in vitro release study. The tip portions of MNs completely dissolved in the rat skin within 5 min after application in vivo. After application of ALN(TIP)–MN in mice, the plasma concentration of ALN rapidly increased, and the bioavailability of ALN was approximately 96%. In addition, the decrease in growth plate was effectively suppressed by this efficient delivery of ALN in a rat model of osteoporosis. Furthermore, no skin irritation was observed after application of ALN(TIP)–MN and subcutaneous injection of ALN, while mild skin irritation was induced by whole-ALN-loaded MN (ALN–MN)—in which ALN is contained in the whole of the micron-scale needles fabricated from hyaluronic acid—and intradermal injection of ALN. These findings indicate that ALN(TIP)–MN is a promising transdermal formulation for the treatment of osteoporosis without skin irritation.

Details

Language :
English
ISSN :
19994923
Volume :
9
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Pharmaceutics
Publication Type :
Academic Journal
Accession number :
edsdoj.099ec5352f04f9499b9f750eea2316b
Document Type :
article
Full Text :
https://doi.org/10.3390/pharmaceutics9030029