Phospholipid‐Free Small Unilamellar Vesicles for Drug Targeting to Cells in the Liver. Issue 43 (6th September 2019)

• Record Type: Journal Article
• Authors: Zhang, Wunan; Böttger, Roland; Qin, Zhu; Kulkarni, Jayesh A.; Vogler, Julian; Cullis, Pieter R.; Li, Shyh‐Dar
• Is Part Of: Small. Volume 15:Issue 43(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-09-06
• Subjects: drug delivery -- liver targeting -- microfluidics -- phospholipid‐free small unilamellar vesicles -- staggered herringbone micromixer; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201901782
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: 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. Abstract : Phospholipid‐free small unilamellar vesicles (PFSUVs) containing TWEEN 80 are manufactured for the first time with a high cholesterol content (83 mol%) using microfluidics. Compared to previously reported surfactant‐based formulations, PFSUVs can retain a transmembrane gradient for active loading of doxorubicin. After intravenous administration, PFSUVs‐doxorubicin is delivered to the liver, predominantly targeting hepatocytes via the endogenous apolipoprotein mechanism.