Microneedle drug eluting balloon for enhanced drug delivery to vascular tissue

Kang Ju Lee; Ji Yong Lee; Seul Gee Lee; Seung Hyun Park; Da Som Yang; Jung Jae Lee; Ali Khademhosseini; Jung Sun Kim; Won Hyoung Ryu

doi:10.1016/j.jconrel.2020.02.012

Microneedle drug eluting balloon for enhanced drug delivery to vascular tissue

Kang Ju Lee, Ji Yong Lee, Seul Gee Lee, Seung Hyun Park, Da Som Yang, Jung Jae Lee, Ali Khademhosseini, Jung Sun Kim, Won Hyoung Ryu

Department of Mechanical Engineering

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

High rates of restenosis and neointimal formation have driven increasing interest in the application of drug eluting balloons (DEB) as counteractive measures for intraluminal drug delivery. The use of DEBs eliminates the need for stents so that serious side effects including in-stent restenosis and stent thrombosis can be avoided and long-term medication of anti-platelet agent is not needed. Despite their benefits, DEBs have poor drug delivery efficiency due to short balloon inflation times (30–60 s) that limit the passive drug diffusion from the balloon surface to the luminal lesion. To increase drug delivery efficiency, a microneedle DEB (MNDEB) was developed by a conformal transfer molding process using a thin polydimethylsiloxane mold bearing a negative array of MNs of 200 μm in height. A MN array composed of UV curable resin was formed onto the surface of DEB, and drugs were coated onto the structure. The mechanical properties of the MN array were investigated and MN penetration into luminal vasculature was confirmed in vivo. An increase in drug delivery efficiency compared to a standard DEB was demonstrated in an in vivo test in a rabbit aorta. Finally, the superior therapeutic efficacy of MNDEBs was evaluated using an atherosclerosis rabbit model.

Original language	English
Pages (from-to)	174-183
Number of pages	10
Journal	Journal of Controlled Release
Volume	321
DOIs	https://doi.org/10.1016/j.jconrel.2020.02.012
Publication status	Published - 2020 May 10

Bibliographical note

Funding Information:
This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) , funded by the Ministry for Health & Welfares, Republic of Korea ( HI08C2149 ), by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIT) ( 2015R1A5A1037668 and 2017R1A2B2003191 ), and by Mid-career Researcher Program through NRF grant funded by the MEST ( 2016R1A2B4010487 ). We specially thank Genoss Co. Ltd. for their generous donation of drug eluting balloons. We would also like to thank Peyton Tebon for his assistance in the revision of this article.

Funding Information:
This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry for Health & Welfares, Republic of Korea (HI08C2149), by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIT) (2015R1A5A1037668 and 2017R1A2B2003191), and by Mid-career Researcher Program through NRF grant funded by the MEST (2016R1A2B4010487). We specially thank Genoss Co. Ltd. for their generous donation of drug eluting balloons. We would also like to thank Peyton Tebon for his assistance in the revision of this article.

Publisher Copyright:
© 2020 Elsevier B.V.

All Science Journal Classification (ASJC) codes

Pharmaceutical Science

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10.1016/j.jconrel.2020.02.012

Cite this

@article{b593addf4ce24178bdbed1e1d743e5af,

title = "Microneedle drug eluting balloon for enhanced drug delivery to vascular tissue",

abstract = "High rates of restenosis and neointimal formation have driven increasing interest in the application of drug eluting balloons (DEB) as counteractive measures for intraluminal drug delivery. The use of DEBs eliminates the need for stents so that serious side effects including in-stent restenosis and stent thrombosis can be avoided and long-term medication of anti-platelet agent is not needed. Despite their benefits, DEBs have poor drug delivery efficiency due to short balloon inflation times (30–60 s) that limit the passive drug diffusion from the balloon surface to the luminal lesion. To increase drug delivery efficiency, a microneedle DEB (MNDEB) was developed by a conformal transfer molding process using a thin polydimethylsiloxane mold bearing a negative array of MNs of 200 μm in height. A MN array composed of UV curable resin was formed onto the surface of DEB, and drugs were coated onto the structure. The mechanical properties of the MN array were investigated and MN penetration into luminal vasculature was confirmed in vivo. An increase in drug delivery efficiency compared to a standard DEB was demonstrated in an in vivo test in a rabbit aorta. Finally, the superior therapeutic efficacy of MNDEBs was evaluated using an atherosclerosis rabbit model.",

author = "Lee, {Kang Ju} and Lee, {Ji Yong} and Lee, {Seul Gee} and Park, {Seung Hyun} and Yang, {Da Som} and Lee, {Jung Jae} and Ali Khademhosseini and Kim, {Jung Sun} and Ryu, {Won Hyoung}",

note = "Funding Information: This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) , funded by the Ministry for Health & Welfares, Republic of Korea ( HI08C2149 ), by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIT) ( 2015R1A5A1037668 and 2017R1A2B2003191 ), and by Mid-career Researcher Program through NRF grant funded by the MEST ( 2016R1A2B4010487 ). We specially thank Genoss Co. Ltd. for their generous donation of drug eluting balloons. We would also like to thank Peyton Tebon for his assistance in the revision of this article. Funding Information: This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry for Health & Welfares, Republic of Korea (HI08C2149), by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIT) (2015R1A5A1037668 and 2017R1A2B2003191), and by Mid-career Researcher Program through NRF grant funded by the MEST (2016R1A2B4010487). We specially thank Genoss Co. Ltd. for their generous donation of drug eluting balloons. We would also like to thank Peyton Tebon for his assistance in the revision of this article. Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",

year = "2020",

month = may,

day = "10",

doi = "10.1016/j.jconrel.2020.02.012",

language = "English",

volume = "321",

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T1 - Microneedle drug eluting balloon for enhanced drug delivery to vascular tissue

AU - Lee, Kang Ju

AU - Lee, Ji Yong

AU - Lee, Seul Gee

AU - Park, Seung Hyun

AU - Yang, Da Som

AU - Lee, Jung Jae

AU - Khademhosseini, Ali

AU - Kim, Jung Sun

AU - Ryu, Won Hyoung

N1 - Funding Information: This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) , funded by the Ministry for Health & Welfares, Republic of Korea ( HI08C2149 ), by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIT) ( 2015R1A5A1037668 and 2017R1A2B2003191 ), and by Mid-career Researcher Program through NRF grant funded by the MEST ( 2016R1A2B4010487 ). We specially thank Genoss Co. Ltd. for their generous donation of drug eluting balloons. We would also like to thank Peyton Tebon for his assistance in the revision of this article. Funding Information: This work was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry for Health & Welfares, Republic of Korea (HI08C2149), by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIT) (2015R1A5A1037668 and 2017R1A2B2003191), and by Mid-career Researcher Program through NRF grant funded by the MEST (2016R1A2B4010487). We specially thank Genoss Co. Ltd. for their generous donation of drug eluting balloons. We would also like to thank Peyton Tebon for his assistance in the revision of this article. Publisher Copyright: © 2020 Elsevier B.V.

PY - 2020/5/10

Y1 - 2020/5/10

N2 - High rates of restenosis and neointimal formation have driven increasing interest in the application of drug eluting balloons (DEB) as counteractive measures for intraluminal drug delivery. The use of DEBs eliminates the need for stents so that serious side effects including in-stent restenosis and stent thrombosis can be avoided and long-term medication of anti-platelet agent is not needed. Despite their benefits, DEBs have poor drug delivery efficiency due to short balloon inflation times (30–60 s) that limit the passive drug diffusion from the balloon surface to the luminal lesion. To increase drug delivery efficiency, a microneedle DEB (MNDEB) was developed by a conformal transfer molding process using a thin polydimethylsiloxane mold bearing a negative array of MNs of 200 μm in height. A MN array composed of UV curable resin was formed onto the surface of DEB, and drugs were coated onto the structure. The mechanical properties of the MN array were investigated and MN penetration into luminal vasculature was confirmed in vivo. An increase in drug delivery efficiency compared to a standard DEB was demonstrated in an in vivo test in a rabbit aorta. Finally, the superior therapeutic efficacy of MNDEBs was evaluated using an atherosclerosis rabbit model.

AB - High rates of restenosis and neointimal formation have driven increasing interest in the application of drug eluting balloons (DEB) as counteractive measures for intraluminal drug delivery. The use of DEBs eliminates the need for stents so that serious side effects including in-stent restenosis and stent thrombosis can be avoided and long-term medication of anti-platelet agent is not needed. Despite their benefits, DEBs have poor drug delivery efficiency due to short balloon inflation times (30–60 s) that limit the passive drug diffusion from the balloon surface to the luminal lesion. To increase drug delivery efficiency, a microneedle DEB (MNDEB) was developed by a conformal transfer molding process using a thin polydimethylsiloxane mold bearing a negative array of MNs of 200 μm in height. A MN array composed of UV curable resin was formed onto the surface of DEB, and drugs were coated onto the structure. The mechanical properties of the MN array were investigated and MN penetration into luminal vasculature was confirmed in vivo. An increase in drug delivery efficiency compared to a standard DEB was demonstrated in an in vivo test in a rabbit aorta. Finally, the superior therapeutic efficacy of MNDEBs was evaluated using an atherosclerosis rabbit model.

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ER -

Microneedle drug eluting balloon for enhanced drug delivery to vascular tissue

Abstract

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