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Effect of Hydrophobic Chain Length in Amphiphilic Chitosan Conjugates on Intracellular Drug Delivery and Smart Drug Release of Redox-Responsive Micelle

Authors :
Yuting Yuan
Wenqiang Tan
Yingqi Mi
Linqing Wang
Zhen Qi
Zhanyong Guo
Source :
Marine Drugs, Vol 22, Iss 1, p 18 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Three redox-sensitive nanocarriers were rationally designed based on amphiphilic low molecular weight chitosan-cystamine-octylamine/dodecylamin/cetylamine (LC-Cys-OA, LC-Cys-DA, LC-Cys-CA) conjugates containing disulfide linkage for maximizing therapeutic effect by regulating hydrophobic interaction. The resultant spherical micelles had the characteristics of low CMC, suitable size, excellent biosafety and desired stability. The drug-loaded micelles were fabricated by embedding doxorubicin (Dox) into the hydrophobic cores. The effect of hydrophobic chain lengths of amphiphilic conjugates on encapsulation capacity, redox sensitivity, trigger-release behavior, cellular uptake efficacy, antitumor effect and antimigratory activity of Dox-loaded micelles was systematically investigated. Studies found that Dox-loaded LC-Cys-CA micelle had superior loading capacity and enhanced redox sensitivity compared with the other two micelles. Release assay indicated that the three Dox-loaded micelles maintained sufficiently stability in normal blood circulation but rapidly disintegrated in tumor cells. More importantly, the LC-Cys-CA micelle with a longer hydrophobic chain length exhibited a higher accumulative Dox release percentage than the other two micelles. Additionally, an increase in hydrophobic chain lengths of amphiphilic conjugates improved cellular uptake efficiency, antitumor effect and antimigration activity of Dox-loaded micelles, which could be explained by enhanced loading ability and redox sensitivity. Our research was expected to provide a viable platform for achieving a desired therapeutic efficacy via the alteration of hydrophobic interaction.

Details

Language :
English
ISSN :
16603397
Volume :
22
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Marine Drugs
Publication Type :
Academic Journal
Accession number :
edsdoj.5316c01d6a24f5495ffb43328ac77cb
Document Type :
article
Full Text :
https://doi.org/10.3390/md22010018