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  • Title: Synthesis, characterization and cytotoxicity of poly(ethylene glycol)-graft-trimethyl chitosan block copolymers.
    Author: Mao S, Shuai X, Unger F, Wittmar M, Xie X, Kissel T.
    Journal: Biomaterials; 2005 Nov; 26(32):6343-56. PubMed ID: 15913769.
    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.
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