Effects of Surface Charge of Inhaled Liposomes on Drug Efficacy and Biocompatibility

<b>Objectives:</b> Liposomes are a promising drug carrier for inhaled delivery systems and their physical parameters could influence therapeutic efficacy significantly. This study was designed to answer the specific question of the proper surface charge of liposomes in pulmonary inhalati...

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Main Authors: Jinniu Zhang, Yun Huang, Wenhao Shen, Yixing Zeng, Yingjing Miao, Nianping Feng, Tianyuan Ci
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/3/329
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author Jinniu Zhang
Yun Huang
Wenhao Shen
Yixing Zeng
Yingjing Miao
Nianping Feng
Tianyuan Ci
author_facet Jinniu Zhang
Yun Huang
Wenhao Shen
Yixing Zeng
Yingjing Miao
Nianping Feng
Tianyuan Ci
author_sort Jinniu Zhang
collection DOAJ
description <b>Objectives:</b> Liposomes are a promising drug carrier for inhaled delivery systems and their physical parameters could influence therapeutic efficacy significantly. This study was designed to answer the specific question of the proper surface charge of liposomes in pulmonary inhalation, as well as to study the synergistic anti-inflammation efficacy between drugs. <b>Methods:</b> In this work, a series of drug-loaded liposomes with different surface charges (from negative to positive) were prepared, and several in vitro and in vivo assays, including cytotoxicity, hemolysis assay, mucus penetration and lipopolysaccharide (LPS)-induced pneumonia model test, were adopted to evaluate the anti-inflammation efficacy and biocompatibility of the above liposomes. <b>Results:</b> Compared with cationic liposomes, anionic liposomes are capable of better mucus penetration and good biocompatibility (low cytotoxicity, better blood compatibility and mild tissue inflammation), but with poor cellular uptake by immune cells. In specific, even when the liposome surface charge was only +2.6 mV, its cytotoxicity and blood hemolysis reached around 20% and 15%, respectively. Furthermore, there was no significant difference in biocompatibility between anionic liposomes (−25.9 vs. −2.5 mV), but a slightly negative-charged liposome exhibited better cellular uptake. <b>Conclusions:</b> Thus, slightly negative-charged liposomes (−1~−3 mV) could be a well inhaled drug carrier considering both efficacy and biocompatibility. In an LPS-induced pneumonia mouse model, the drug-loaded liposomes achieved better anti-inflammatory efficacy compared with free drugs.
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spelling doaj-art-8b5a00a151ff437a9887168307a78c932025-08-20T02:42:24ZengMDPI AGPharmaceutics1999-49232025-03-0117332910.3390/pharmaceutics17030329Effects of Surface Charge of Inhaled Liposomes on Drug Efficacy and BiocompatibilityJinniu Zhang0Yun Huang1Wenhao Shen2Yixing Zeng3Yingjing Miao4Nianping Feng5Tianyuan Ci6School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaSchool of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China<b>Objectives:</b> Liposomes are a promising drug carrier for inhaled delivery systems and their physical parameters could influence therapeutic efficacy significantly. This study was designed to answer the specific question of the proper surface charge of liposomes in pulmonary inhalation, as well as to study the synergistic anti-inflammation efficacy between drugs. <b>Methods:</b> In this work, a series of drug-loaded liposomes with different surface charges (from negative to positive) were prepared, and several in vitro and in vivo assays, including cytotoxicity, hemolysis assay, mucus penetration and lipopolysaccharide (LPS)-induced pneumonia model test, were adopted to evaluate the anti-inflammation efficacy and biocompatibility of the above liposomes. <b>Results:</b> Compared with cationic liposomes, anionic liposomes are capable of better mucus penetration and good biocompatibility (low cytotoxicity, better blood compatibility and mild tissue inflammation), but with poor cellular uptake by immune cells. In specific, even when the liposome surface charge was only +2.6 mV, its cytotoxicity and blood hemolysis reached around 20% and 15%, respectively. Furthermore, there was no significant difference in biocompatibility between anionic liposomes (−25.9 vs. −2.5 mV), but a slightly negative-charged liposome exhibited better cellular uptake. <b>Conclusions:</b> Thus, slightly negative-charged liposomes (−1~−3 mV) could be a well inhaled drug carrier considering both efficacy and biocompatibility. In an LPS-induced pneumonia mouse model, the drug-loaded liposomes achieved better anti-inflammatory efficacy compared with free drugs.https://www.mdpi.com/1999-4923/17/3/329inhalationliposomesurface chargepneumoniaanti-inflammation
spellingShingle Jinniu Zhang
Yun Huang
Wenhao Shen
Yixing Zeng
Yingjing Miao
Nianping Feng
Tianyuan Ci
Effects of Surface Charge of Inhaled Liposomes on Drug Efficacy and Biocompatibility
Pharmaceutics
inhalation
liposome
surface charge
pneumonia
anti-inflammation
title Effects of Surface Charge of Inhaled Liposomes on Drug Efficacy and Biocompatibility
title_full Effects of Surface Charge of Inhaled Liposomes on Drug Efficacy and Biocompatibility
title_fullStr Effects of Surface Charge of Inhaled Liposomes on Drug Efficacy and Biocompatibility
title_full_unstemmed Effects of Surface Charge of Inhaled Liposomes on Drug Efficacy and Biocompatibility
title_short Effects of Surface Charge of Inhaled Liposomes on Drug Efficacy and Biocompatibility
title_sort effects of surface charge of inhaled liposomes on drug efficacy and biocompatibility
topic inhalation
liposome
surface charge
pneumonia
anti-inflammation
url https://www.mdpi.com/1999-4923/17/3/329
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