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Carboxymethyl Chitosan Modified Oxymatrine Liposomes for the Alleviation of Emphysema in Mice via Pulmonary Administration
- Source :
- Molecules, Vol 27, Iss 11, p 3610 (2022)
- Publication Year :
- 2022
- Publisher :
- MDPI AG, 2022.
-
Abstract
- Pulmonary emphysema is a fatal lung disease caused by the progressive thinning, enlargement and destruction of alveoli that is closely related to inflammation and oxidative stress. Oxymatrine (OMT), as a bioactive constituent of traditional Chinese herbal Sophora flavescens, has great potential to alleviate pulmonary emphysema via its anti-inflammatory and antioxidative activities. Pulmonary administration is the most preferable way for the treatment of lung diseases. To improve the in vivo stability and pulmonary retention of OMT, OMT-loaded liposome with carboxymethyl chitosan (CMCS) modification was developed. The CMCS was modified on the surface of OMT liposomes via electrostatic attraction and covalent conjugation to obtain Lipo/OMT@CMCS and CMCS-Lipo/OMT, respectively. A porcine pancreatic elastase (PPE)-induced emphysema mice model was established to evaluate the alleviation effects of OMT on alveolar expansion and destruction. CMCS-modified liposomal OMT exhibited superior ameliorative effects on emphysema regardless of the preparation methods, and higher sedimentation and longer retention in the lung were observed in the CMCS-Lipo group. The mechanisms of OMT on emphysema were related to the downregulation of inflammatory cytokines and the rebalancing of antioxidant/oxidation via the Nrf2/HO-1 and NF-κB/IκB-α signaling pathways, leading to reduced cell apoptosis. Moreover, the OMT liposomal preparations further enhanced its anti-inflammatory and antioxidative effects. In conclusion, pulmonary administration of OMT is a potential strategy for the treatment of emphysema and the therapeutic effects can be further improved by CMCS-modified liposomes.
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 27
- Issue :
- 11
- Database :
- Directory of Open Access Journals
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7fa4e71e8ac0473eb461514e0019ab70
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/molecules27113610