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The synthesis and physico-chemical characterisation of a biodegradable multiblock polymer drug carrier based on poly(ethylene glycol) (PEG) is described. The blocks of PEG ( M w 2,000) are connected by an enzymatically degradable tripeptide derivative consisting of one lysine and two glutamic acid residues. Doxorubicin (Dox), was attached to the polymer carrier via a hydrazone bond susceptible to acid hydrolysis at pH 5.0. Human immunoglobulin (IgG) was covalently linked to the polymer-Dox conjugate by the reaction of 2-pyridyldisulfanyl groups of the polymer with thiol groups of the antibody modified with 2-iminothiolane. The resulting antibody-polymer-drug conjugates were characterised by size-exclusion chromatography, UV/VIS spectrophotometry, electrophoresis and amino acid analysis. All polymers studied (both with and without IgG) showed high anti-proliferative activity against concanavalin A-stimulated murine splenocytes and various cancer cell lines in vitro. The polymer-Dox conjugate (without IgG) exhibited a significant anti-tumor efficacy against murine EL4 T-cell lymphoma and human colorectal carcinoma SW620 in vivo.
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Pechar et al. (2005) studied this question.
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