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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

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-sc...

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Autores principales: Katsumi, Hidemasa, Tanaka, Yutaro, Hitomi, Kaori, Liu, Shu, Quan, Ying-shu, Kamiyama, Fumio, Sakane, Toshiyasu, Yamamoto, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620570/
https://www.ncbi.nlm.nih.gov/pubmed/28817072
http://dx.doi.org/10.3390/pharmaceutics9030029
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author Katsumi, Hidemasa
Tanaka, Yutaro
Hitomi, Kaori
Liu, Shu
Quan, Ying-shu
Kamiyama, Fumio
Sakane, Toshiyasu
Yamamoto, Akira
author_facet Katsumi, Hidemasa
Tanaka, Yutaro
Hitomi, Kaori
Liu, Shu
Quan, Ying-shu
Kamiyama, Fumio
Sakane, Toshiyasu
Yamamoto, Akira
author_sort Katsumi, Hidemasa
collection PubMed
description 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.
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spelling pubmed-56205702017-10-03 Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis Katsumi, Hidemasa Tanaka, Yutaro Hitomi, Kaori Liu, Shu Quan, Ying-shu Kamiyama, Fumio Sakane, Toshiyasu Yamamoto, Akira Pharmaceutics Article 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. MDPI 2017-08-17 /pmc/articles/PMC5620570/ /pubmed/28817072 http://dx.doi.org/10.3390/pharmaceutics9030029 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Katsumi, Hidemasa
Tanaka, Yutaro
Hitomi, Kaori
Liu, Shu
Quan, Ying-shu
Kamiyama, Fumio
Sakane, Toshiyasu
Yamamoto, Akira
Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis
title Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis
title_full Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis
title_fullStr Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis
title_full_unstemmed Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis
title_short Efficient Transdermal Delivery of Alendronate, a Nitrogen-Containing Bisphosphonate, Using Tip-Loaded Self-Dissolving Microneedle Arrays for the Treatment of Osteoporosis
title_sort efficient transdermal delivery of alendronate, a nitrogen-containing bisphosphonate, using tip-loaded self-dissolving microneedle arrays for the treatment of osteoporosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620570/
https://www.ncbi.nlm.nih.gov/pubmed/28817072
http://dx.doi.org/10.3390/pharmaceutics9030029
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