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Ascorbic acid-modified brain-specific liposomes drug delivery system with "lock-in" function.
Wenjiao Xiao1, Qiuyi Fu1, Yi Zhao1
1Key Laboratory of Drug Targeting and Drug Delivery System of Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, 610041, PR China.
Chemistry and Physics of Lipids
|January 21, 2019
Summary
A novel ascorbic acid (AA) derivative liposome enhances drug delivery to the brain by targeting glucose transporter 1 (GLUT1) and vitamin C transporters. This system significantly boosts docetaxel brain concentration for improved central nervous system (CNS) therapy.
Area of Science:
- Neuroscience
- Biotechnology
- Pharmacology
Background:
- Effective drug delivery to the brain is a major challenge in treating central nervous system (CNS) disorders.
- Targeting specific transporters like glucose transporter 1 (GLUT1) and Na+-dependent vitamin C transporter (SVCT2) offers a potential strategy for enhanced brain penetration.
- Ascorbic acid (AA) derivatives can be utilized as ligands for targeted liposome delivery systems.
Purpose of the Study:
- To design and synthesize a novel brain-targeting liposome using an ascorbic acid (AA) derivative with a "lock-in" function.
- To evaluate the efficacy of these liposomes in enhancing the brain delivery of docetaxel (DTX).
- To investigate the role of GLUT1 and SVCT2 transporters in the targeted delivery mechanism.
Main Methods:
- Synthesis and characterization of AA-derivative-functionalized liposomes.
- Evaluation of liposome properties: particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis, and cytotoxicity.
- In vivo studies to assess brain targeting and drug concentration of docetaxel delivered via liposomes compared to controls.
- Pharmacokinetic analysis to determine the efficiency of the delivery system.
Main Results:
- The developed AA-thiamine disulfide system (TDS)-coated liposomes demonstrated improved brain targeting ability.
- Significant increase in docetaxel (DTX) brain concentration was observed with TDS-coated liposomes compared to naked DTX, non-coated, and AA-coated liposomes.
- Relative uptake efficiency and concentration efficiency were enhanced by 3.24- and 5.62-fold, respectively, compared to naked docetaxel.
- In vivo data confirmed enhanced distribution and pharmacokinetic parameters for CNS drug delivery.
Conclusions:
- The ascorbic acid thiamine disulfide (AA-TDS) delivery system is a promising carrier for enhancing drug delivery into the brain.
- Liposomes functionalized with AA derivatives can effectively utilize GLUT1 and SVCT2 for targeted brain delivery.
- This novel liposomal system holds potential for improving the therapeutic efficacy of drugs targeting the central nervous system (CNS).