目的 合成(4-羧丁基)三苯基溴化膦［(4-carboxybutyl)triphenylphosphonium bromide，TPP］修饰的糖原（glycogen，Gly）衍生物（Gly-TPP），以其制备包载黄芩苷（baicalin，BA）的糖原纳米粒（BA/Gly-TPP NPs），并对其进行制剂学表征。方法 通过酯化反应将TPP连接到Gly上，合成线粒体靶向的树状大分子糖原衍生物Gly-TPP，通过核磁共振氢谱、紫外光谱、红外光谱确定其结构，通过细胞毒性实验考察其安全性。利用糖原内核包载疏水性药物黄芩苷，构建线粒体靶向的给药系统BA/Gly-TPP NPs，考察其粒径、载药量、体外释放、粒径稳定性等制剂学性质。结果 成功合成的Gly-TPP呈现规则的球形，无细胞毒性。BA/Gly-TPP NPs粒径分布在70～80 nm，ζ电位为（8.84±0.89）mV，载药量为（20.67±0.16）%，同时具有良好的释药行为。结论 Gly-TPP具有良好的载药性能，为纳米药物载体系统的设计提供了新思路。

Objective To synthesize (4-carboxybutyl) triphenylphosphonium bromide (TPP) modified glycogen (Gly), prepare baicalin (BA) loaded glycogen nanoparticles (BA/Gly-TPP NPs), and investigate the physicochemical properties of the nanoparticles. Methods TPP was linked to Gly through an esterification reaction to synthesize mitochondrial targeting dendritic macromolecular nanoparticles Gly-TPP NPs. The structure was determined by ¹H-NMR, UV and IR spectra, and the safety was tested by cytotoxicity test. Then, BA was encapsulated into Gly-TPP to construct a drug delivery system BA/Gly-TPP NPs. Particle size, drug loading, in vitro release and particle size stability of the nanoparticles were investigated. Results Gly-TPP was successfully synthesized and showed regular sphericity and no cytotoxic. BA/Gly-TPP NPs had regular spherical shape with mean particle size of about 70-80 nm, ζ potential of (8.84 ±0.89) mV, drug loading of (20.67 ±0.16)%, and a good drug release behavior. Conclusion Gly-TPP shows good performance for drug delivery, which will provide a new choice for the design of nanocarrier delivery system.

R283.6

国家重点研发计划项目（2021YFC2103100）；江苏省自然科学基金资助项目（BK20201344）