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Molecular Dynamics Simulations Reveal Octanoylated Hyaluronic Acid Enhances Liposome Stability, Stealth and Targeting.
Zhu, Jingyi; Xu, Limei; Wang, Wenxin; Xiao, Min; Li, Jian; Wang, Lushan; Jiang, Xukai.
Affiliation
  • Zhu J; State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Qingdao 266237, China.
  • Xu L; State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Qingdao 266237, China.
  • Wang W; Shandong Institute for Food and Drug Control, Jinan 250000, China.
  • Xiao M; State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Qingdao 266237, China.
  • Li J; Biomedicine Discovery Institute, Monash University, Melbourne 3800, Australia.
  • Wang L; State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Qingdao 266237, China.
  • Jiang X; State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Qingdao 266237, China.
ACS Omega ; 9(31): 33833-33844, 2024 Aug 06.
Article in En | MEDLINE | ID: mdl-39130542
ABSTRACT
Liposome-based drug delivery systems have been widely used in drug and gene delivery. However, issues such as instability, immune clearance, and poor targeting have significantly limited their clinical utility. Consequently, there is an urgent need for innovative strategies to improve liposome performance. In this study, we explore the interaction mechanisms of hyaluronic acid (HA), a linear anionic polysaccharide composed of repeating disaccharide units of d-glucuronic acid and N-acetyl-d-glucosamine connected by alternating ß-1,3 and ß-1,4 glycosidic linkages, and its octanoylated derivates (OHA) with liposomes using extensive coarse-grained molecular dynamics simulations. The octyl moieties of OHA spontaneously inserted into the phospholipid bilayer of liposomes, leading to their effective coating onto the surface of liposome and enhancing their structural stability. Furthermore, encapsulating liposome with OHA neutralized their surface potential, interfering with the formation of a protein corona known to contribute to liposomal immune clearance. Importantly, the encapsulated OHA maintained its selectivity and therefore targeting ability for CD44, which is often overexpressed in tumor cells. These molecular-scale findings shed light on the interaction mechanisms between HA and liposomes and will be useful for the development of next-generation liposome-based drug delivery systems.

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: ACS Omega Year: 2024 Document type: Article Affiliation country: China Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: ACS Omega Year: 2024 Document type: Article Affiliation country: China Country of publication: United States