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Synthesis, characterization and cytotoxicity of poly(ethylene glycol)-graft-trimethyl chitosan block copolymers

Paper ID Volume ID Publish Year Pages File Format Full-Text
12089 777 2005 14 PDF Available
Title
Synthesis, characterization and cytotoxicity of poly(ethylene glycol)-graft-trimethyl chitosan block copolymers
Abstract

PEGylated trimethyl chitosan (TMC) copolymers were synthesized in an attempt to both increase the solubility of chitosan in water, and improve the biocompatibility of TMC. A series of copolymers with different degrees of substitution were obtained by grafting activated poly(ethylene glycol)s (PEG) of different MW onto TMC via primary amino groups. Structure of the copolymers was characterized using 1H, 13C NMR spectroscopy and GPC. Solubility experiments demonstrated that PEG-g-TMC copolymers were completely water-soluble over the entire pH range of 1–14 regardless of the PEG MW, even when the graft density was as low as 10%. Using the methyl tetrazolium (MTT) assay, the effect of TMC molecular weight, PEGylation ratio, PEG and TMC molecular weight in the copolymers, and complexation with insulin on the cytotoxicity of TMC was examined, and IC50 values were calculated with L929 cell line. All polymers exhibited a time- and dose-dependent cytotoxic response that increased with molecular weight. PEGylation can decrease the cytotoxicity of TMC to a great extent in the case of low molecular weight TMCs. According to the cytotoxicity results, PEG 5 kDa is superior for PEGylation when compared to PEG 550 Da at similar graft ratios. Complexation with insulin further increased cell viability. In addition, Lactate dehydrogenase (LDH) assays were performed to quantify the membrane-damaging effects of the copolymers, which is in line with the conclusion drawn from MTT assay. Moreover, the safety of the copolymers was corroborated by observing the morphological change of the cells with inverted phase contrast microscopy. Based upon these results PEG-g-TMC merits further investigations as a drug delivery vehicle.

Keywords
Trimethyl chitosan; PEGylation; Copolymer; In vitro cytotoxicity; MTT assay; LDH assay
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Synthesis, characterization and cytotoxicity of poly(ethylene glycol)-graft-trimethyl chitosan block copolymers
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 26, Issue 32, November 2005, Pages 6343–6356
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