Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes
Xiaojia Liu,1,2 Caiyan Lin,1 Wenfei Zhong,1 Zhongwen Yuan,1 Pengke Yan,1 Shixia Guan2 1Department of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliat...
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| Format: | Article |
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Dove Medical Press
2023-08-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/effective-attenuation-of-arteriosclerosis-following-lymphatic-targeted-peer-reviewed-fulltext-article-IJN |
| _version_ | 1797766960873734144 |
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| author | Liu X Lin C Zhong W Yuan Z Yan P Guan S |
| author_facet | Liu X Lin C Zhong W Yuan Z Yan P Guan S |
| author_sort | Liu X |
| collection | DOAJ |
| description | Xiaojia Liu,1,2 Caiyan Lin,1 Wenfei Zhong,1 Zhongwen Yuan,1 Pengke Yan,1 Shixia Guan2 1Department of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Pengke Yan; Shixia Guan, Email gysyypk@126.com; drguan@gzucm.edu.cnBackground: The activation of lymphatic vessel function is the crux to resolving atherosclerosis (AS), a chronic inflammatory disease. Rapamycin (RAPA) recently has attracted considerable attention as a potent drug to induce atherosclerotic plaque attenuation. The objective of this work was to develop a ligand-decorated, RAPA-loaded liposome for lymphatic-targeted delivery of drugs to improve abnormal lymphatic structure and function, resulting in highly effective regression of atherosclerotic plaques.Methods: Hyaluronic acid-decorated, RAPA-loaded liposomes (HA-RL) were fabricated by emulsion-solvent evaporation. The average size, zeta potential, entrapment efficiency were characterized, and the stability and drug release in vitro were investigated. Furthermore, the in vitro and in vivo lymphatic targeting ability were evaluated on lymphatic endothelial cells and LDLR−/− mice, and the efficiency of this nano-system in inducing the attenuation of atherosclerotic plaques was confirmed.Results: HA-RL had a size of 100 nm, over 90% drug encapsulation efficiency, the storage stability was distinguished, demonstrating a slow release from the lipid nano-carriers. The mean retention time (MRT) and elimination half-life (t1/2β) achieved from HA-RL were 100.27± 73.08 h and 70.74± 50.80 h, respectively. HA-RL acquired the most prominent efficacy of lymphatic-targeted delivery and atherosclerotic plaques attenuation, implying the successful implementation of this novel drug delivery system in vivo.Conclusion: HA-RL exhibited the most appreciable lymphatic targeting ability and best atherosclerotic plaques attenuation efficiency, opening a new paradigm and promising perspective for the treatment of arteriosclerosis.Keywords: rapamycin, hyaluronic acid, lymphatic targeting, arteriosclerosis, liposomes |
| first_indexed | 2024-03-12T20:32:50Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-03-12T20:32:50Z |
| publishDate | 2023-08-01 |
| publisher | Dove Medical Press |
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| series | International Journal of Nanomedicine |
| spelling | doaj.art-fcd43f81f308435e8881c5b0d362940d2023-08-01T19:38:38ZengDove Medical PressInternational Journal of Nanomedicine1178-20132023-08-01Volume 184403441985604Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin LiposomesLiu XLin CZhong WYuan ZYan PGuan SXiaojia Liu,1,2 Caiyan Lin,1 Wenfei Zhong,1 Zhongwen Yuan,1 Pengke Yan,1 Shixia Guan2 1Department of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Pengke Yan; Shixia Guan, Email gysyypk@126.com; drguan@gzucm.edu.cnBackground: The activation of lymphatic vessel function is the crux to resolving atherosclerosis (AS), a chronic inflammatory disease. Rapamycin (RAPA) recently has attracted considerable attention as a potent drug to induce atherosclerotic plaque attenuation. The objective of this work was to develop a ligand-decorated, RAPA-loaded liposome for lymphatic-targeted delivery of drugs to improve abnormal lymphatic structure and function, resulting in highly effective regression of atherosclerotic plaques.Methods: Hyaluronic acid-decorated, RAPA-loaded liposomes (HA-RL) were fabricated by emulsion-solvent evaporation. The average size, zeta potential, entrapment efficiency were characterized, and the stability and drug release in vitro were investigated. Furthermore, the in vitro and in vivo lymphatic targeting ability were evaluated on lymphatic endothelial cells and LDLR−/− mice, and the efficiency of this nano-system in inducing the attenuation of atherosclerotic plaques was confirmed.Results: HA-RL had a size of 100 nm, over 90% drug encapsulation efficiency, the storage stability was distinguished, demonstrating a slow release from the lipid nano-carriers. The mean retention time (MRT) and elimination half-life (t1/2β) achieved from HA-RL were 100.27± 73.08 h and 70.74± 50.80 h, respectively. HA-RL acquired the most prominent efficacy of lymphatic-targeted delivery and atherosclerotic plaques attenuation, implying the successful implementation of this novel drug delivery system in vivo.Conclusion: HA-RL exhibited the most appreciable lymphatic targeting ability and best atherosclerotic plaques attenuation efficiency, opening a new paradigm and promising perspective for the treatment of arteriosclerosis.Keywords: rapamycin, hyaluronic acid, lymphatic targeting, arteriosclerosis, liposomeshttps://www.dovepress.com/effective-attenuation-of-arteriosclerosis-following-lymphatic-targeted-peer-reviewed-fulltext-article-IJNrapamycinlipsomeshyaluronic acidlymphatic targetingarteriosclerosis |
| spellingShingle | Liu X Lin C Zhong W Yuan Z Yan P Guan S Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes International Journal of Nanomedicine rapamycin lipsomes hyaluronic acid lymphatic targeting arteriosclerosis |
| title | Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes |
| title_full | Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes |
| title_fullStr | Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes |
| title_full_unstemmed | Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes |
| title_short | Effective Attenuation of Arteriosclerosis Following Lymphatic-Targeted Delivery of Hyaluronic Acid-Decorated Rapamycin Liposomes |
| title_sort | effective attenuation of arteriosclerosis following lymphatic targeted delivery of hyaluronic acid decorated rapamycin liposomes |
| topic | rapamycin lipsomes hyaluronic acid lymphatic targeting arteriosclerosis |
| url | https://www.dovepress.com/effective-attenuation-of-arteriosclerosis-following-lymphatic-targeted-peer-reviewed-fulltext-article-IJN |
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