葡萄糖基聚膦腈水凝胶的制备

通过对葡萄糖的羟基引入保护基再与聚二氯磷腈反应后用强酸脱保护制得侧链含部分葡萄糖基的聚膦腈,然后测量聚合物与植物外源凝集素ConA混合溶液的透光率的变化来研究凝胶化过程.结果表明,在ConA的浓度相同的情况下,聚合物溶液的浓度越大,越容易形成凝胶;第二取代基团的水溶性好,葡萄糖的侧基比例大,有益于凝胶的形成.

PREPARATION OF GLUCOSYL-SUBSTITUTED POLYPHOSPHAZENE HYDROGELS

Two kinds of polyphosphazenes,that bear α-D-glucosyl side groups together with methoxyethoxy or ethyl glycinato as cosubstituent groups,have been synthesized and characterized by IR and ~1H-NMR analyses.They were examined in order to investigate their possible use as matrix for glucose-sensitive insulin delivery basing on the specific interaction of glucose with lection. Briefly, the polymers were prepared via nucleophilic displacement of the reactive chlorines of polydichlorophosphazene with diisopropylidene D-glucose at first, and subsequently with methoxyethanol (polymer a) or glycine ethyl ester (polymer b) to substitute the residual P-Cl. After filtration and dialysis, the purified polymers were then treated with 90% trifluoroacetic acid to remove isopropylidene groups to get glucosyl groups. The formation of aggregates of glucosyl-substituted polyphosphazenes physically crosslinked by Concanavalin A (Con A) was studied by monitoring the transmittance at 360 nm of dilute polymeric aqueous solutions. Hydrogels were made by mixing concentrated glucosyl-substituted polyphosphazene aqueous solution with Con A aqueous solution. Different polyphosphazenes with various compositions of α-D-glucosyl side group and methoxyethoxy or ethyl glycinato side group combinations were obtained by adjusting the feeding dose of the nucleophiles. And their hydrophilicity differed from each other for the methoxyethoxy group is hydrophilic, and the ethyl glycinato group is hydrophobic, which would affect the formation of hydrogel and the drug release thereof in different way. In the deprotection reaction, the treating time needed to be prolonged to complete the hydrolysis of isopropylidene groups, however, it would cause significant cleavage of polyphosphazene backbones and degradation of cosubstituted ethyl glycinato groups (while almost no effect to methoxyethoxy) in the strong acidic condition. As a result, the deprotection ratio of glucoses was maintained at about 60% in this study to avoid remarkable decrease in molecular weight, and at the same time, the remained diisopropylidene D-glucosyl groups were considered biocompatible and might play a role in balancing polymeric hydrophilicity/hydrophobicity. Con A is one of the most widely used lectins in studying the interaction of specific saccharide with protein, particularly, for nonreducing D-mannosyl and D-glucosyl residues. For both polymers a and b, their dilute solutions rapidly turned turbid when Con A was mixed into, and turbidity increased with increasing the concentration of polymeric solutions and the content of glucosyl side groups in the polymers due to the formation of more and larger aggregates. The aggregates could be dissociated by addition of free glucose, and transmittance of the solution increased. On the other hand, it has been found that the transmittance data of solutions of polymer a mixed with Con A were much larger that those of polymer b, even if they had the similar amount of glucosyl side groups and the same polymeric concentration. One possible reason for this phenomenon was that polymer b could not dissolve well in water due to the presence of hydrophobic ethyl glycinato side groups, and the interaction between Con A and glucosyl groups was hindered. Thus, hydrogels were made from polymer a and Con A by increasing the polymeric concentration above 10 wt%. Higher concentrations of glucosyl-substituted polyphosphazene, more hydrophilic co-substituted side groups and higher amounts of glucosyl side groups would be in favor of hydrogel formation. This hydrogel can be a potential matrix for glusoce-sensitive insulin delivery.