Zwitterionic inhaler with synergistic therapeutics for reprogramming of M2 macrophage to pro‐inflammatory phenotype
Zwitterionic inhaler with synergistic therapeutics for reprogramming of M2 macrophage to pro‐inflammatory phenotype
Myriad lung diseases are life threatening and macrophages play a key role in both physiological and pathological processes. Macrophages have each pro-/anti-inflammatory phenotype, and each lung disease can be aggravated by over-polarized macrophage. Therefore, development of a method capable of mediating the macrophage phenotype is one of the solutions for lung disease treatment. For mediating the phenotype of macrophages, the pulmonary delivery system (PDS) is widely used due to its advantages, such as high efficiency and accessibility of the lungs. However, it has a low drug delivery efficiency ironically because of the perfect lung defense system consisting of the mucus layer and airway macrophages. In this study, zwitterion-functionalized poly(lactide-co-glycolide) (PLGA) inhalable microparticles (ZwPG) are synthesized to increase the efficiency of the PDS. The thin layer of zwitterions formed on PLGA surface has high nebulizing stability and show high anti-mucus adhesion and evasion of macrophages. As a reprogramming agent for macrophages, ZwPG containing dexamethasone (Dex) and pirfenidone (Pir) are treated to over-polarized M2 macrophages. As a result, a synergistic effect of Dex/Pir induces reprogramming of M2 macrophage to pro-inflammatory phenotypes.
anti-macrophage uptake, anti-mucus, drug delivery, macrophage reprogramming, synergistic therapeutics, zwitterionic inhalers
Jung, Sungwon
371206f7-2fc1-4a27-b95b-160bcf972380
Heo, Sungeun
46e8e68f-34ab-4ef4-9ebf-f784d70e8837
Oh, Yoogyeong
900c84c8-aef3-417d-be9d-1cfdac996346
Park, Kyungtae
6e840e43-b35f-4493-a8b8-ede69f7bfa49
Park, Sohyeon
199a3b1d-eac0-4d93-a82d-83b073e93cb5
Choi, Woojin
b33cff38-9da2-41f7-b855-159bc86b1521
Kim, Yang-Hee
de0d641b-c2cb-4e73-9ae2-e20d33689f5d
Jung, Se Yong
86f7cabf-0b1b-425f-ba96-e0dc8725074a
Hong, Jinkee
2f392f3c-fae3-4fdf-9736-2a7eb6c1b10e
1 September 2023
Jung, Sungwon
371206f7-2fc1-4a27-b95b-160bcf972380
Heo, Sungeun
46e8e68f-34ab-4ef4-9ebf-f784d70e8837
Oh, Yoogyeong
900c84c8-aef3-417d-be9d-1cfdac996346
Park, Kyungtae
6e840e43-b35f-4493-a8b8-ede69f7bfa49
Park, Sohyeon
199a3b1d-eac0-4d93-a82d-83b073e93cb5
Choi, Woojin
b33cff38-9da2-41f7-b855-159bc86b1521
Kim, Yang-Hee
de0d641b-c2cb-4e73-9ae2-e20d33689f5d
Jung, Se Yong
86f7cabf-0b1b-425f-ba96-e0dc8725074a
Hong, Jinkee
2f392f3c-fae3-4fdf-9736-2a7eb6c1b10e
Jung, Sungwon, Heo, Sungeun, Oh, Yoogyeong, Park, Kyungtae, Park, Sohyeon, Choi, Woojin, Kim, Yang-Hee, Jung, Se Yong and Hong, Jinkee
(2023)
Zwitterionic inhaler with synergistic therapeutics for reprogramming of M2 macrophage to pro‐inflammatory phenotype.
Advanced Healthcare Materials, 12 (22), [2300226].
(doi:10.1002/adhm.202300226).
Abstract
Myriad lung diseases are life threatening and macrophages play a key role in both physiological and pathological processes. Macrophages have each pro-/anti-inflammatory phenotype, and each lung disease can be aggravated by over-polarized macrophage. Therefore, development of a method capable of mediating the macrophage phenotype is one of the solutions for lung disease treatment. For mediating the phenotype of macrophages, the pulmonary delivery system (PDS) is widely used due to its advantages, such as high efficiency and accessibility of the lungs. However, it has a low drug delivery efficiency ironically because of the perfect lung defense system consisting of the mucus layer and airway macrophages. In this study, zwitterion-functionalized poly(lactide-co-glycolide) (PLGA) inhalable microparticles (ZwPG) are synthesized to increase the efficiency of the PDS. The thin layer of zwitterions formed on PLGA surface has high nebulizing stability and show high anti-mucus adhesion and evasion of macrophages. As a reprogramming agent for macrophages, ZwPG containing dexamethasone (Dex) and pirfenidone (Pir) are treated to over-polarized M2 macrophages. As a result, a synergistic effect of Dex/Pir induces reprogramming of M2 macrophage to pro-inflammatory phenotypes.
Text
ZwPG_Revised Manuscript_AHM
- Accepted Manuscript
More information
Accepted/In Press date: 3 April 2023
e-pub ahead of print date: 11 May 2023
Published date: 1 September 2023
Additional Information:
Funding Information:
This research was supported by Korea‐England Cooperative Development Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF‐2021K1A3A1A88100035) and UK Medical Research Council (MC_PC_21012), Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2019M3A9H1103786), Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HN21C1410000021, Republic of Korea) and faculty research grant of Yonsei University College of Medicine (6‐2020‐0098).
Keywords:
anti-macrophage uptake, anti-mucus, drug delivery, macrophage reprogramming, synergistic therapeutics, zwitterionic inhalers
Identifiers
Local EPrints ID: 477764
URI: http://eprints.soton.ac.uk/id/eprint/477764
ISSN: 2192-2659
PURE UUID: 31502d01-1f13-41f6-a3fc-c90baa5986d6
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Date deposited: 14 Jun 2023 16:36
Last modified: 15 Aug 2024 01:47
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Contributors
Author:
Sungwon Jung
Author:
Sungeun Heo
Author:
Yoogyeong Oh
Author:
Kyungtae Park
Author:
Sohyeon Park
Author:
Woojin Choi
Author:
Se Yong Jung
Author:
Jinkee Hong
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