壳聚糖/乙酰半胱氨酸纳米粒子的性质及体外释药性

制备了一种基于壳聚糖/乙酰半胱氨酸偶合物(CS-NAC)的新型巯基纳米粒子并进行了结构表征, 同时对纳米粒子的黏附性、溶胀性和药物释放进行了测试. 结果表明, 纳米粒子具有较小的粒径(140~210 nm)和正的表面电位(19.5~31.7 mV), 胰岛素的载药量达到13%~42%. 这些性质随着巯基含量的变化而变化. 与壳聚糖纳米粒子相比, 巯基壳聚糖纳米粒子表现出了更强更快的黏附性质. 体外释放研究结果表明, 巯基壳聚糖纳米粒子的胰岛素释放具有pH响应性. 在pH=6.8时, 15 min即能释放58.6 %的胰岛素; 而在pH=5.4时, 24 h内仅有不到40%的胰岛素被释放. 因此, CS-NAC纳米粒子用于胰岛素的黏膜给药体系具有很好的应用前景.

Properties and in vitro Evaluation of Chitosan-NAC Nanoparticle for Drug Release

Nanoparticles have received much attention in the development of transmucosal administration because of the special nano-effectivity. On the basis of the formation of disulphide bonds between thiol groups on polymer and cysteine-rich domains of mucus glycoproteins, the thiolated nanoparticles as carriers can prolong the residence time of drugs on the nasal mucosa and allow a sustained drug release at a given target site. In this study, a novel nanoparticle containing N-acetyl-L-cysteine-g-chitosan conjugate(CS-NAC) was prepared and characterized. Mucoadhesive and swelling properties of CS-NAC conjugates were evaluated in vitro. Release studies were performed with insulin as the model drug. The resulting insulin-loaded CS-NAC nanopartilces had a diameter of 140—210 nm, positive zeta potential values(19.5—31.7 mV) and insulin loading(13%—42%). The physicochemical properties of nanoparticles were affected by the amount of thiol groups. The thiolated chitosan nanoparticles exhibited much higher and faster mucoadhesion than unmodified chitosan nanoparticles. In vitro release studies demonstrate that the insulin-loaded CS-NAC nanopartilces was pH-sensitive delivery systems. At pH=6.8, 58.6% of insulin was released from CS-NAC4 nanoparticles within 15 min, while less than 40% of insulin was release with 24 h at pH=5.4. Therefore, the novel thiolated chitosan nanoparticle appears to be a very promising vehicle for transmucosal insulin drug delivery.