Glycopolymers for Biomedical Applications

Abstract

Glycopolymers are synthetic polymers containing carbohydrate groups. They may play an important role in a wide range of biomolecular events such as adhesion, inflammation, cellular recognition, cell growth regulation, and cancer cell metastasis. They may play an important role in a wide range of biomolecular events such as adhesion, inflammation, cellular recognition, cell growth regulation, and cancer cell metastasis. In this study, three glycopolymers were synthesized and their application as biomedical materials was evaluated. In the first project, a glycomonomer with amide linkage: (maleic acid monoamido)-2-D-glucopyranose (MAMG) was first synthesized within a one-step reaction in 4 h with relatively high yield. The product was isolated by precipitation in ethyl acetate. Copolymerization of MAMG and styrene was conducted in DMSO using AIBN as initiator with different initial monomer ratios. 1H-NMR was used to characterize the chemical structure of MAMG. The chemical structure of copolymer PMAMG-ST was confirmed by FTIR and 1H-NMR. Molecular weight and final monomer ratio on PMAMG-ST was determined by GPC and elemental analysis, respectively. The biodecomposition and release of the sugar of glycomonomer, glycopolymer and control sample was evaluated by an oxidative-fermentative test. In the second project, glucosamine was grafted onto poly(vinyl methyl ether-alt-maleic acid) to produce a glycopolymer, Glu-PMVE-MAc, with high yield. The product was isolated by precipitation in ethyl acetate. The chemical structure of the glycopolymer was confirmed by FTIR and 1H-NMR. Elemental analysis was utilized to determine the amount of grafted glucosamine groups. Glu-PMVE-MAc was crosslinked by poly(ethylene glycol) (PEG 400 or PEG 600). Swelling of the Glu-PMVE-MAc hydrogels in aqueous solution at pH of 1.2 to 7.4 was investigated. The mesh size of the hydrogels was calculated from swelling data using Peppas–Merrill equation. The drug delivery profile of fluorescein isothiocyanate-dextran (FITC-dextran)-loaded hydrogels in enzyme-free simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8) was studied. In the third project, a thermo-responsive amphiphilic glycopolymer: poly(2-{[(D-glucosamine-2N-yl)carbonyl]-oxy}ethylmethacrylate)-b-poly(propylene oxide) (PHEMAGI-PPO) was synthesized via atom transfer radical polymerization (ATRP). The chemical structure of glycomonomer (HEMAGI), macroinitiator (PPO-Br), and glycopolymer was confirmed by 1H-NMR or 13C-NMR spectra. Degree of functionalization of PPO-Br was determined to be more than 99%. Molecular weight of glycopolymers was estimated from integral ratio of specific peaks on NMR spectra. The critical micelle concentration (CMC) of the glycopolymer was measured by dye micellization method and the diameter of the formed micelles was determined by transmission electron microscopy (TEM). The lectin recognition property was evaluated using Con A as a model lectin.