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Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient drug delivery system for cancer therapy

Paper ID Volume ID Publish Year Pages File Format Full-Text
636 53 2013 13 PDF Available
Title
Doxorubicin-loaded amphiphilic polypeptide-based nanoparticles as an efficient drug delivery system for cancer therapy
Abstract

An amphiphilic anionic copolymer, methoxy poly(ethylene glycol)-b-poly(l-glutamic acid-co-l-phenylalanine) (mPEG-b-P(Glu-co-Phe)), with three functionalized domains, was synthesized and used as a nanovehicle for cationic anticancer drug doxorubicin hydrochloride (DOX·HCl) delivery via electrostatic interactions for cancer treatment. The three domains displayed distinct functions: PEG block chain for prolonged circulation; poly(phenylalanine) domain for stabilizing the nanoparticle construct through hydrophobic/aromatic interactions; and the poly(glutamic acid) domain for providing electrostatic interactions with the cationic drug to be loaded. The copolymer could self-assemble into micellar-type nanoparticles, and DOX was successfully loaded into the interior of nanoparticles by simple mixing of DOX·HCl and the copolymer in the aqueous phase. DOX-loaded mPEG-b-P(Glu-co-Phe) nanoparticles (DOX-NP) had a superior drug-loading content (DLC) (21.7%), a high loading efficiency (almost 98%) and a pH-triggered release of DOX. The size of DOX-NP was ∼140 nm, as determined by dynamic light scattering measurements and transmission electron microscopy. In vitro assays showed that DOX-NP exhibited higher cell proliferation inhibition and higher cell uptake in A549 cell lines compared with free DOX·HCl. Maximum tolerated dose (MTD) studies showed that DOX-NP demonstrated an excellent safety profile with a significantly higher MTD (15 mg DOX kg−1) than that of free DOX·HCl (5 mg DOX kg−1). The in vivo studies on the subcutaneous non-small cell lung cancer (A549) xenograft nude mice model confirmed that DOX-NP showed significant antitumor activity and reduced side effects, and then enhanced tumor accumulation as a result of the prolonged circulation in blood and the enhanced permeation and retention effect, compared with free DOX, indicating its great potential for cancer therapy.

Graphical abstractAmphiphilic polypeptide-based complex nanoparticles formed by anionic methoxy poly(ethylene glycol)-b-poly(l-glutamic acid-co-l-phenylalanine) and cationic anticancer drug doxorubicin hydrochloride were developed as an efficient drug delivery system for cancer therapy with enhanced therapeutic efficacy and reduced systemic toxicity.Figure optionsDownload full-size imageDownload high-quality image (73 K)Download as PowerPoint slide

Keywords
Poly(amino acids); Doxorubicin hydrochloride; Electrostatic interaction; pH sensitive; Drug delivery
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 9, Issue 12, December 2013, Pages 9330–9342
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