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A multilayered cell culture model for transport study in solid tumors: Evaluation of tissue penetration of polyethyleneimine based cationic micelles

Paper ID Volume ID Publish Year Pages File Format Full-Text
32127 44902 2014 10 PDF Available
Title
A multilayered cell culture model for transport study in solid tumors: Evaluation of tissue penetration of polyethyleneimine based cationic micelles
Abstract

•Cationic micelles showed a noticeable distribution in a multilayered cell culture.•Penetration occurred against convective flow caused by a hydraulic pressure gradient.•Most of cationic micelles penetrated as unimers via intracellular pathways.•Clathrin-mediated endocytosis and macropinocytosis are seemingly responsible for penetration.

Limited drug distribution is partially responsible for the efficacy gap between preclinical and clinical studies of nano-sized drug carriers for cancer therapy. In this study, we examined the transport behavior of cationic micelles formed from a triblock copolymer of poly(d,l-lactide-co-glycolide)-block-branched polyethyleneimine-block-poly(d,l-lactide-co-glycolide) using a unique in vitro tumor model composed of a multilayered cell culture (MCC) and an Ussing chamber system. The Cy3-labeled cationic micelles showed remarkable Cy3 distribution in the MCC whereas charge-shielded micelles with a poly(ethylene glycol) surface accumulated on the surface of the MCC. Penetration occurred against convectional flow caused by a hydraulic pressure gradient. The study using fluorescence resonance energy transfer (FRET) showed that the cationic micelles dissociate at the interface between the culture media and the MCC or possibly inside of the first-layer cells and penetrates into the MCC as unimers. The penetration and distribution were energy-dependent and suppressed by various endocytic inhibitors. These suggest that cationic unimers mainly utilized clathrin-mediated endocytosis and macropinocytosis for cellular entry and a significant fraction were exocytosed by an unknown mechanism.

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Keywords
Intratumoral distribution; Penetration; Multilayered cell culture; Micelle; Cationic surface; Endocytosis
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A multilayered cell culture model for transport study in solid tumors: Evaluation of tissue penetration of polyethyleneimine based cationic micelles
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Publisher
Database: Elsevier - ScienceDirect
Journal: - Volume 9, Issue 6, December 2014, Pages 695–704
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us