Phospholipid‐Free Small Unilamellar Vesicles for Drug Targeting to Cells in the Liver

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.

Human spermbots for patient-representative 3D ovarian cancer cell treatment

“…To analyze drug-loading efficiency, we compared two different methods: firstly, an indirect method, analyzing the ratio of the initially added drug concentration to the drug concentration remaining in the supernatant after loading at a defined number of sperm, and secondly, a direct method that measured the DOX-HCl amount after extraction from the sperm following a Triton-X and acidified isopropanol-based procedure as reported elsewhere. 29 These methods were applied to healthy donor and patient sperm samples, obtaining relevant statistical analysis, which allowed us to define the localization of drug within sperm for the first time. The drug amount in both cases was determined with a fluorescence spectrophotometer by measuring the autofluorescence of DOX-HCl (for details see Methods section).…”

“…Secondly, we used a direct method following a protocol reported elsewhere. 29 Briefly, DOX-HCl-loaded sperm were purified 3 times and redispersed in SP-TALP. The dispersion was incubated at 37 °C with Triton-X 100 (4%) for 30 min for complete cell lysis.…”

Simultaneous Chromatographic Quantitation of Drug Substance and Excipients in Nanoformulations Using a Combination of Evaporative Light Scattering and Absorbance Detectors

“…Niosomes were prepared by staggered herringbone microfluidics using the NanoAssemblr Benchtop system (Precision Nanosystems Inc., Vancouver, BC, Canada) as described previously with modifications . TWEEN 80 (25 mol%), Chol (70.0–74.5 mol%), and Cur (0.5–5.0 mol%) were dissolved in ethanol at a total lipid concentration of 10 mg/mL.…”

Oral Delivery of Biologics in Inflammatory Bowel Disease Treatment

“…The biodistribution study showed a minimized systemic exposure with low accumulation in the liver ( Wang et al, 2020 ). Liposomes and other bilayer structure vesicles ( Lee and Feijen, 2012 ; Akbarzadeh et al, 2013 ; Zhang et al, 2019 ) are broadly applied for drug delivery purposes. Jung Min Kim and others reported a series of infliximab-loaded liposomes for oral IBD treatment.…”