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Bioreducible poly(amidoamine)s as carriers for intracellular protein delivery to intestinal cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
7626 558 2012 10 PDF Available
Title
Bioreducible poly(amidoamine)s as carriers for intracellular protein delivery to intestinal cells
Abstract

An effective intracellular protein delivery system was developed based on linear poly(amidoamine)s (PAAs) that form self-assembled cationic nanocomplexes with oppositely charged proteins. Two differently functionalized PAAs were synthesized by Michael-type polyaddition of 4-amino-1-butanol (ABOL) to cystamine bisacrylamide (CBA) and to bisacryloylpiperazine (BAP), yielding p(CBA-ABOL) and p(BAP-ABOL), respectively. These water-soluble PAAs efficiently condense human serum albumin (HSA) by self-assembly into stable nanoscaled and positively-charged complexes. The disulfide-containing p(CBA-ABOL)/HSA nanocomplexes exhibited high mucoadhesive properties and, while stable under neutral (extracellular) conditions, rapidly destabilized in a reductive (intracellular) environment due to the cleavage of the repetitive disulfide linkages in the CBA units of the polymer. Human-derived intestinal Caco-2/TC7 cells and HT29-MTX mucus secreting cells were exposed to these PAAs/HSA nanoparticles and the extent of their uptake and the localization within endosomal compartments were examined. The higher uptake of p(CBA-ABOL)/HSA than that of p(BAP-ABOL)/HSA suggests that the mucoadhesive properties of the p(CBA-ABOL) are beneficial to the uptake process. The transported HSA was located within early endosomes, lysosomes and the cytosol. The enhanced uptake of the p(CBA-ABOL)/HSA nanoparticles, observed in the presence of Cyclosporin A, a non-specific Multi Drug Resistance (MDR) blocker, indicates the possible efflux of these nanoparticles through MDR transporters. The results show that bioreducible PAAs have excellent properties for intracellular protein delivery, and should be applicative in oral protein delivery.

Keywords
Poly(amidoamine); Intracellular protein delivery; Mucoadhesive nanoparticles; Bioresponsive nanoparticles; Bioreducible polymer; Endosomal uptake
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Bioreducible poly(amidoamine)s as carriers for intracellular protein delivery to intestinal cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 2, January 2012, Pages 614–623
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