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Inhalable nitric oxide delivery systems for pulmonary arterial hypertension treatment

Inhalable nitric oxide delivery systems for pulmonary arterial hypertension treatment
Inhalable nitric oxide delivery systems for pulmonary arterial hypertension treatment
Pulmonary arterial hypertension (PAH) is a severe medical condition characterized by elevated blood pressure in the pulmonary arteries. Nitric oxide (NO) is a gaseous signaling molecule with potent vasodilator effects; however, inhaled NO is limited in clinical practice because of the need for tracheal intubation and the toxicity of high NO concentrations. In this study, inhalable NO-releasing microspheres (NO inhalers) are fabricated to deliver nanomolar NO through a nebulizer. Two NO inhalers with distinct porous structures are prepared depending on the molecular weights of NO donors. It is confirmed that pore formation can be controlled by regulating the migration of water molecules from the external aqueous phase to the internal aqueous phase. Notably, open porous NO inhalers (OPNIs) can deliver NO deep into the lungs through a nebulizer. Furthermore, OPNIs exhibit vasodilatory and anti-inflammatory effects via sustained NO release. In conclusion, the findings suggest that OPNIs with highly porous structures have the potential to serve as tools for PAH treatment.
nebulizer, nitric oxide, pulmonary arterial hypertension, pulmonary delivery
1613-6810
Oh, Yoogyeong
900c84c8-aef3-417d-be9d-1cfdac996346
Park, Kyungtae
6e840e43-b35f-4493-a8b8-ede69f7bfa49
Jung, Sungwon
371206f7-2fc1-4a27-b95b-160bcf972380
Choi, Moonhyun
2218ecd8-d884-4d81-84c2-bad4852838c9
Kim, Taihyun
02f8a921-dd77-40b5-a087-685e37cf4ca3
Lee, Yoojin
76f3e3e1-cc10-47d0-98cb-7c4864ce13da
Choi, Jae Young
bff4caab-02b2-4032-93c0-67e4d0979106
Kim, Yang-Hee
de0d641b-c2cb-4e73-9ae2-e20d33689f5d
Jung, Se Yong
72f046c4-c6b8-4127-aca5-1affb1eadd9c
Hong, Jinkee
2f392f3c-fae3-4fdf-9736-2a7eb6c1b10e
Oh, Yoogyeong
900c84c8-aef3-417d-be9d-1cfdac996346
Park, Kyungtae
6e840e43-b35f-4493-a8b8-ede69f7bfa49
Jung, Sungwon
371206f7-2fc1-4a27-b95b-160bcf972380
Choi, Moonhyun
2218ecd8-d884-4d81-84c2-bad4852838c9
Kim, Taihyun
02f8a921-dd77-40b5-a087-685e37cf4ca3
Lee, Yoojin
76f3e3e1-cc10-47d0-98cb-7c4864ce13da
Choi, Jae Young
bff4caab-02b2-4032-93c0-67e4d0979106
Kim, Yang-Hee
de0d641b-c2cb-4e73-9ae2-e20d33689f5d
Jung, Se Yong
72f046c4-c6b8-4127-aca5-1affb1eadd9c
Hong, Jinkee
2f392f3c-fae3-4fdf-9736-2a7eb6c1b10e

Oh, Yoogyeong, Park, Kyungtae, Jung, Sungwon, Choi, Moonhyun, Kim, Taihyun, Lee, Yoojin, Choi, Jae Young, Kim, Yang-Hee, Jung, Se Yong and Hong, Jinkee (2023) Inhalable nitric oxide delivery systems for pulmonary arterial hypertension treatment. Small, [2308936]. (doi:10.1002/smll.202308936).

Record type: Article

Abstract

Pulmonary arterial hypertension (PAH) is a severe medical condition characterized by elevated blood pressure in the pulmonary arteries. Nitric oxide (NO) is a gaseous signaling molecule with potent vasodilator effects; however, inhaled NO is limited in clinical practice because of the need for tracheal intubation and the toxicity of high NO concentrations. In this study, inhalable NO-releasing microspheres (NO inhalers) are fabricated to deliver nanomolar NO through a nebulizer. Two NO inhalers with distinct porous structures are prepared depending on the molecular weights of NO donors. It is confirmed that pore formation can be controlled by regulating the migration of water molecules from the external aqueous phase to the internal aqueous phase. Notably, open porous NO inhalers (OPNIs) can deliver NO deep into the lungs through a nebulizer. Furthermore, OPNIs exhibit vasodilatory and anti-inflammatory effects via sustained NO release. In conclusion, the findings suggest that OPNIs with highly porous structures have the potential to serve as tools for PAH treatment.

Text
Manuscript_Inhalable_Nitric_Oxide_Releasing_Microspheres_with_Controlled_Porous_Structure_to_Reverse_Vascular_Remodeling_in_Pulmonary_Arterial_Hypertension (1) - Accepted Manuscript
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Accepted/In Press date: 24 January 2023
Published date: 6 December 2023
Additional Information: Funding Information: Y.O. and J.H. developed the research plan, and Y.O. carried out the experiments and acquired the data. K.P., S.J., and M.C. worked on the figures and contributed to the writing of the manuscript. T.K., Y.L., and J.C. provided technical support. Y.K., S.J., and J.H. supervised the project. All authors discussed and edited the manuscript. The authors wish to thank the Flow Cytometry Core Facility in Yonsei University College of Medicine, for technical assistance. This research was supported by the Korea Drug Development Fund funded by the Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HN21C1410000021, Republic of Korea), Korea‐England Cooperative Development Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF‐2021K1A3A1A88100035), National Research Foundation of Korea(NRF) grant funded by the Korea government (MSIT) (RS‐2023‐00212494), a faculty research grant of Yonsei University College of Medicine (6‐2018‐0139) and UK medical research council (MC_PC_21012). Publisher Copyright: © 2023 Wiley-VCH GmbH.
Keywords: nebulizer, nitric oxide, pulmonary arterial hypertension, pulmonary delivery

Identifiers

Local EPrints ID: 485518
URI: http://eprints.soton.ac.uk/id/eprint/485518
ISSN: 1613-6810
PURE UUID: 3b73f2ce-37d3-4170-9f7c-89f14cc2a8e4
ORCID for Yang-Hee Kim: ORCID iD orcid.org/0000-0002-5312-3448

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Date deposited: 07 Dec 2023 17:42
Last modified: 06 Dec 2024 05:01

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Contributors

Author: Yoogyeong Oh
Author: Kyungtae Park
Author: Sungwon Jung
Author: Moonhyun Choi
Author: Taihyun Kim
Author: Yoojin Lee
Author: Jae Young Choi
Author: Yang-Hee Kim ORCID iD
Author: Se Yong Jung
Author: Jinkee Hong

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