目的 制备坎地沙坦（CD）-雷公藤红素（CEL）共载还原敏感胶束，并对其进行制剂学评价。方法 以合成的具有还原敏感性的透明质酸-胱氨-CD（HCCD）作为聚合物材料，透明质酸-1,6-己二胺-CD（HHCD）作为非还原敏感对照，单因素法进行制备方法、溶剂、CEL与HCCD质量比的筛选，制备HHCD、HCCD、HHCD/CEL、HCCD/CEL 4种聚合物胶束。采用芘-丙酮法测定样品的临界胶束浓度；应用电位粒径测定仪分析各胶束粒径、聚合物分散性指数（PDI）、Zeta电位； HPLC法检测载药量、包封率；透射电镜法观察形态；进行各胶束储存稳定性、血浆稳定性、冻干粉复溶稳定性考察及溶血情况考察；考察0、10 μmol·L^-1、10、20 mmol·L^-1谷胱甘肽（GSH）对胶束粒径的影响；考察在含0、10 μmol·L^-1、10、20 mmol·L^-1 GSH的释放介质中HHCD/CEL、HCCD/CEL体外释放行为。结果 制备的HHCD、HCCD的临界胶束浓度值约为4.5 μg·mL^-1，4种胶束的粒径在200 nm左右，PDI均小于0.2，且分布较为均匀； 4种聚合物胶束的电位分别为-24.7、-29.2、-25.9、-32.1 mV； 4种胶束的载药量和包封率分别在8.9%和73%以上； 4种胶束的形态均呈类球形，稳定性良好，不发生溶血； HHCD/CEL胶束在浓度为0、10 μmol·L^-1、10、20 mmol·L^-1的GSH条件下粒径均无明显变化，而HCCD/CEL胶束在GSH的浓度为10、20 mmol·L^-1时粒径发生明显的变化；在GSH浓度为0、10 μmol·L^-1时，2种聚合物胶束中的药物在48 h内的释放量均在21%左右。在GSH的浓度为10 mmol·L^-1时，HCCD/CEL中的2种药物在24 h内累积释放量分别为40%、50%左右；在GSH浓度为20 mmol·L^-1时，HCCD/CEL中的药物CD、CEL在24 h时累积释放量达到70%左右，48 h时达到80%左右。结论 制备的还原敏感性胶束HCCD/CEL具有良好的稳定性、还原敏感性。

Objective To prepare redox-sensitive prodrug micelles co-loaded with candesartan (CD) and celastrol (CEL) and evaluate their pharmaceutical properties. Methods The synthesized hyaluronic acid-cystamine-candesartan (HCCD) with reductive sensitivity was used as the polymer material, and hyaluronic acid-1,6-hexanediamine-candesartan (HHCD) was used as the non-reductive sensitive control. The preparation method, solvent, and the mass ratio of CEL to HCCD were screened by the single-factor method to prepare four types of polymer micelles: HHCD, HCCD, HHCD/CEL, and HCCD/CEL. The critical micelle concentration (CMC) of the samples was determined by the pyrene-acetone method. The particle size, polydispersity index (PDI), and Zeta potential of each micelle were analyzed by a particle size analyzer. The drug loading and encapsulation efficiency were detected by HPLC. The morphology was observed by transmission electron microscopy. The storage stability, plasma stability, and reconstitution stability of the freeze-dried powder of each micelle were investigated, as well as the hemolysis situation. The effects of 0, 10 μmol·L^-1, 10, and 20 mmol·L^-1 glutathione (GSH) on the particle size of the micelles were investigated. The in vitro release behaviors of HHCD/CEL and HCCD/CEL in release media containing 0, 10 μmol·L^-1, 10, and 20 mmol·L^-1 GSH were also investigated. Results The CMC values of HHCD and HCCD were approximately 4.5 μg·mL^-1. The particle sizes of the four types of micelles were around 200 nm, and the PDI was less than 0.2, with a relatively uniform distribution. The potentials of the four types of micelles were -24.7, -29.2, -25.9, and -32.1 mV, respectively. The drug loading and encapsulation efficiency of the four types of micelles were above 8.9% and 73%, respectively. The morphologies of the four types of micelles were all spherical-like, with good stability and no hemolysis. The particle size of HHCD/CEL micelles did not change significantly under GSH concentrations of 0, 10 μmol·L^-1, 10, and 20 mmol·L^-1, while the particle size of HCCD/CEL micelles changed significantly at GSH concentrations of 10 and 20 mmol·L^-1. At GSH concentrations of 0 and 10 μmol·L^-1, the cumulative release of the two drugs in the two types of micelles within 48 h was approximately 21%. At a GSH concentration of 10 mmol·L^-1, the cumulative release of the two drugs in HCCD/CEL within 24 h was approximately 40% and 50%, respectively. At a GSH concentration of 20 mmol·L^-1, the cumulative release of CD and CEL in HCCD/CEL reached approximately 70% and 80% within 24 h and 48 h, respectively. Conclusion The prepared reductive-sensitive micelles HCCD/CEL have good stability and reductive sensitivity.

河南省科技攻关项目（232102311178， 252102311282）；河南省高等学校重点科研项目（24A350002， 25B350003）；开封市科技攻关项目（2403002）