聚L-谷氨酸/壳聚糖纳米凝胶的制备与表征

Preparation and Characterization of Poly(L-glutamic acid)/Chitosan Nanogels

以纳米SiO_2为模板,在其表面接枝聚L-谷氨酸(PLGA),以壳聚糖(CS)为大分子交联剂,构建了PLGA/CS化学交联中空纳米凝胶,研究了纳米SiO_2粒子表面接枝,纳米凝胶制备、微观形貌以及pH响应行为。以水溶性盐酸米托蒽醌(MTX)为模型药物,研究了PLGA/CS纳米凝胶的载药与释药性能。结果表明,PLGA在SiO_2表面成功接枝;PLGA/CS纳米凝胶呈球形,平均粒径为365 nm。冻干后纳米凝胶尺寸收缩至100 nm左右;PLGA/CS纳米凝胶具有pH响应性,随pH的提高,PLGA/CS纳米凝胶粒径先减小后增大;PLGA/CS纳米凝胶对MTX有良好的负载能力,最高载药量达41.4%。载MTX的PLGA/CS纳米凝胶在起始阶段存在一定程度突释,随后释药速度明显变缓,直到7 d后达到释放平衡,药物缓释效果良好。

The SiO_2 nanospheres with good monodispersity were successfully prepared by St9 ber method. And poly（L-glutamic acid）（PLGA） was grafted to the surface. PLGA/CS hollow nanogels were obtained using chitosan（CS） as macromolecular crosslinking agent. Then,the PLGA/CS nanogels were obtained after SiO_2 core removal. The preparation,micromorphology,pH-responsiveness,drug loading capacity and release of PLGA/CS hollow nanogels were characterized by nuclear magnetic resonance（NMR） spectroscopy,infrared（IR） spectroscopy,light scattering,and transmission electron microscopy（TEM）. Taking water-soluble antineoplastic agent mitoxantrone（MTX） as model drug,the drug loading and release performance were characterized by confocal laser scanning microscopy（CLSM） and ultraviolet visible spectrophotometer（UV-vis）. The results show that PLGA is successfully grafted onto the surface of SiO_2 nanospheres. The PLGA/CS nanogels are spherical in shape and uniform in particle size. The average diameter is about 365 nm.After freeze-drying,the size of PLGA/CS nanogels is shrinked to ca. 100 nm. The PLGA/CS nanogels show pH-dependent behavior. With the increase of pH,the particle size decreases first and then increases. PLGA/CS nanogels display high loading capacity of MTX with the maximum value of 41.4%,which is mainly attributed to the electrostatic interaction between MTX and-COO-. The PLGA/CS nanogels show sustained release behavior. The MTX-loaded PLGA/CS nanogels show a certain degree of burst release at the initial stage,and then the release rate is slowed down and finally reaches equilibrium after 7 d.