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Pyridylhydrazone-based PEGylation for pH-reversible lipopolyplex shielding

Paper ID Volume ID Publish Year Pages File Format Full-Text
7591 557 2011 12 PDF Available
Title
Pyridylhydrazone-based PEGylation for pH-reversible lipopolyplex shielding
Abstract

PEGylation, which is reversed after the therapeutic agent reaches the target cell, presents an attractive feature for drug, protein or nucleic acid delivery. For bioreversible surface shielding of DNA lipopolyplexes, the bifunctional, endosomal pH-cleavable reagent OPSS-PEG-HZN-Chol [ω-2-pyridyldithio poly (ethylene) glycol α-(butyraldehyde) (N1-cholesteryloxycarbonyl-1, 2-diaminoethane amidocarboxy) pyridyl hydrazone] was synthesized. Both OPSS-PEG-HZN-Chol and its corresponding pH stable analog OPSS-PEG-Chol form micelles which remain stable and shielded at pH 7.4 and 37 °C as demonstrated by size exclusion chromatography. At endosomal pH 5.4, OPSS-PEG-HZN-Chol micelles are destroyed within 30 min at 37 °C, while OPSS-PEG-Chol micelles remain stable. Lipopolyplexes composed of DNA condensed with polyethylenimine (PEI), phospholipids including dioleoyl phosphatidylethanolamine (DOPE) and pH-labile OPSS-PEG-HZN-Chol were prepared by the ethanol injection technique. The optimal formulation yielded particles of 160 nm size and a zeta potential of +7 mV. At physiological neutral conditions pyridylhydrazone-based PEGylated lipopolyplexes were as stable as standard PEGylated lipopolyplexes. At pH 5.4, an increase in size was observed only for pH-reversible HZN lipopolyplexes. Transfection with plasmids encoding for luciferase or EGFP resulted in an upto 40-fold enhancement in gene expression with the reversibly PEGylated lipopolyplexes compared to the stably PEGylated ones. Incorporation of a synthetic peptidic ligand for transferrin receptor targeting further improved transfection efficiency in transferrin overexpressing tumor cells. Cellular association and uptake studies by flow cytometry and confocal laser scanning microscopy with an Alexa-labeled PEG shield revealed intracellular deshielding in case of the HZN lipopolyplexes.

Keywords
Lipopolyplex; pH-reversible; Cholesteryl hydrazone; Deshielding; PEG
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Pyridylhydrazone-based PEGylation for pH-reversible lipopolyplex shielding
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 3, January 2011, Pages 858–869
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