高偶合巯基壳聚糖的合成和体外评价

Synthesis and in vitro evaluation of high-density chitosan thioglycolic acid conjugate

目的:用新合成法合成较高巯基含量的壳聚糖巯基醋酸偶合物,并进一步评价其各项性能。方法:用碳化二亚胺和N-羟基磺酸基丁二酰亚胺的活化,提高巯基醋酸与壳聚糖共价偶合率。用重量法考察本产物的溶胀性能,用离体的猪肠黏膜上皮测定膜黏附性,通过溶菌酶实验考察降解性能,并采用单层Caco-2细胞为模版测定14C-甘露糖醇在壳聚糖巯基醋酸偶合物作用下的渗透性能等。结果:本合成法所得巯基壳聚糖的巯基含量可达7·56%,总黏附功是未经修饰聚合物的16·3倍,偶合物的溶胀行为和未经修饰的聚合物在同一范围内,而且高偶合巯基壳聚糖也可被溶菌酶生物降解。结论:巯基含量的增加可提高壳聚糖巯基醋酸偶合物的多项生物学性能。高偶合巯基壳聚糖是新型给药系统中很有前景的功能性敷料。

Objective： To synthesize and characterize the high-density chitosan thioglycolic acid conjugates （CTAC）. Methods： Catalyzed by carbodiimide and N-hydroxysulfosuccinimide （NHS）, thioglycolic acid （TGA） was covalently coupled to chitosan. The CTAC viscosity across freshly excised porcine intestinal mucosa was measured. The dilatancy of the conjugates was determined by using gravimetry. The biodegradation was studied via a reaction with lysozyme. The permeability was evaluated based on the quantity of radiolabeled ^14 C-mannitol across the Caco-2 cell monolayer. Results：A total yield of the high-density CTAC was 7.56%. The viscosity was displayed 16-fold higher than the raw chitosan. No significant difference of the CTAC dilatancy from the raw chitosan was found. The CTAC could be biodegraded by the lysozyme. The CTAC permeability was much more improved compared with the raw chitosan. Conclusion： Due to the highdensity thiol groups existed in the conjugates, the CTAC has better physiochenncal behaviors. The CTAC potentiates to be used to more sophisticated drug delivery systems as a new exeipient.