Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783267614004346880 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5620570 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT katsumihidemasa efficienttransdermaldeliveryofalendronateanitrogencontainingbisphosphonateusingtiploadedselfdissolvingmicroneedlearraysforthetreatmentofosteoporosis AT tanakayutaro efficienttransdermaldeliveryofalendronateanitrogencontainingbisphosphonateusingtiploadedselfdissolvingmicroneedlearraysforthetreatmentofosteoporosis AT hitomikaori efficienttransdermaldeliveryofalendronateanitrogencontainingbisphosphonateusingtiploadedselfdissolvingmicroneedlearraysforthetreatmentofosteoporosis AT liushu efficienttransdermaldeliveryofalendronateanitrogencontainingbisphosphonateusingtiploadedselfdissolvingmicroneedlearraysforthetreatmentofosteoporosis AT quanyingshu efficienttransdermaldeliveryofalendronateanitrogencontainingbisphosphonateusingtiploadedselfdissolvingmicroneedlearraysforthetreatmentofosteoporosis AT kamiyamafumio efficienttransdermaldeliveryofalendronateanitrogencontainingbisphosphonateusingtiploadedselfdissolvingmicroneedlearraysforthetreatmentofosteoporosis AT sakanetoshiyasu efficienttransdermaldeliveryofalendronateanitrogencontainingbisphosphonateusingtiploadedselfdissolvingmicroneedlearraysforthetreatmentofosteoporosis AT yamamotoakira efficienttransdermaldeliveryofalendronateanitrogencontainingbisphosphonateusingtiploadedselfdissolvingmicroneedlearraysforthetreatmentofosteoporosis |