小尺寸低聚壳聚糖/丹参酮ⅡA纳米载药体系

New Tanshinone ⅡA Delivery System Using Chitosan Nanomicelles of Small Size

纳米载药系统以其独特的化学性质已广泛应用于小分子药物转运,并已有相关的临床实例报道[1~6].壳聚糖（CS）因其所特有的无生物毒性、易生物降解和良好生物相容性等优点而备受关注[7~16].由于传统方法制备的壳聚糖纳米颗粒粒径高达数百纳米,使其生物利用度低,限制了其更广泛应用.我们在前期工作中发现：一种无残留合成方法可以制备粒径在50~80 nm的小尺寸低聚壳聚糖纳米载体，并可携带药物高效穿透细胞膜，显著提高药效．

It is still a great challenge to design and synthesize ultra-small chitosan nanoparticles for encapsulating highly hydrophobic neuroprotectants,such as anti-stroke drug tanshinone IIA. To address the issue,a new amphiphilic polymeric micelle system（ i. e. CS-g-TPS） was synthesized by covalent linking of D-α-tocopherol succinic acid ester with hydroxylethyl-chitosan in a green and effective approach. The results showed that the obtained CS-g-TPS can be self-assembled into ultra-small nanoparticles by hydrophilichydrophobic interaction in aqueous solution,which can be effectively loaded with tanshinone IIA. The particle size and morphology were characterized by scanning electron microscopy（ SEM） and dynamic light scattering（ DLS）,respectively. Bioassays of cell viability and drug uptake further revealed that the CS-g-TPS /tanshinone IIA delivery system could achieve excellent in vitro biocompatibility,as well as high cellular uptake efficiency. It indicated that CS-g-TPS might be a promising drug delivery system for water insoluble neuroprotectant with the characteristics of high biosafety.