Phospholipid‐Free Small Unilamellar Vesicles for Drug Targeting to Cells in the Liver
| Autor: | Wunan Zhang, Jayesh A. Kulkarni, Zhu Qin, Roland Böttger, Pieter R. Cullis, Shyh-Dar Li, Julian Vogler |
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| Rok vydání: | 2019 |
| Předmět: |
Phospholipid
02 engineering and technology 010402 general chemistry 01 natural sciences Polyethylene Glycols Biomaterials chemistry.chemical_compound Drug Delivery Systems polycyclic compounds medicine Animals Tissue Distribution General Materials Science Doxorubicin Lipid bilayer Phospholipids Unilamellar Liposomes Mice Inbred BALB C Cholesterol Vesicle Bilayer technology industry and agriculture General Chemistry 021001 nanoscience & nanotechnology Endocytosis 3. Good health 0104 chemical sciences medicine.anatomical_structure Liver Receptors LDL chemistry Hepatocyte Drug delivery Biophysics Female lipids (amino acids peptides and proteins) 0210 nano-technology Biotechnology medicine.drug |
| Zdroj: | Small. 15:1901782 |
| ISSN: | 1613-6829 1613-6810 |
| Popis: | It is reported that cholesterol (Chol) and TWEEN 80 at a molar ratio of 5:1 can form small unilamellar vesicles (SUVs) using a staggered herringbone micromixer. These phospholipid-free SUVs (PFSUVs) can be actively loaded with a model drug for targeting hepatocytes via the endogenous apolipoprotein mechanism. PFSUVs particles with compositions of Chol:TWEEN 80 ranging between 1.5:1 and 5:1 (mol/mol) can be produced with a mean diameter of ≈80 nm, but only the high-Chol formulations (3:1 and 5:1) can retain a transmembrane gradient of ammonium sulfate for active loading of doxorubicin (DOX). Under cryo-transmission electron microscopy, PFSUVs-DOX displays a unilamellar bilayer structure with DOX molecules forming spindle-shape aggregates inside the aqueous core. Relative to PEGylated liposomal doxorubicin (PLD) that exhibits little interaction with cells in various conditions, the cellular uptake of PFSUVs-DOX is dependent on the presence of serum and enhanced with an increased concentration of apolipoproteins. After intravenous injection, the vast majority of PFSUVs-DOX accumulates in the liver and DOX is detected in all liver cells (predominantly the hepatocytes), while PLD is captured only by the sinusoidal cells (i.e., macrophages). This report discloses an innovative lipid bilayer vesicle for highly efficient and selective hepatocyte targeting. |
| Databáze: | OpenAIRE |
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