Abstract：
Our study aimed at developing polymer micelles that possess redox sensitivity and excellent controlled release properties. 3,3\'-dithiodipropionic acid (DTDPA, Abbreviation in synthetic polymers: SS) was introduced as ROS (Reactive oxygen species)response bond and connecting arm to couple hydroxyethyl starch (HES) with oleanolic acid (OA), resulting in the synthesis of four distinct grafting ratios of HES-SS-OA. FTIR (Fourier Transform infrared spectroscopy) and 1H NMR (1H Nuclear magnetic resonance spectra) were used to verify the triumphant combination of HES-SS-OA. Polymer micelles were found to encapsulate OA in an amorphous form, as indicated by the results of XRD (X-ray diffraction) and DSC (Differential scanning calorimetry). When the OA grafting rate on HES increased from 7.72 % to 11.75 %, the particle size decreased from 297.79 nm to 201.39 nm as the polymer micelles became compact due to enhanced hydrophobicity. In addition, the zeta potential changed from -16.42 mv to -25.78 mv, the PDI (polydispersity index) decreased from 0.3649 to 0.2435, and the critical micelle concentration (CMC) decreased from 0.0955 mg/mL to 0.0123 mg/mL. Results of erythrocyte hemolysis, cytotoxicity and cellular uptake illustrated that HES-SS-OA had excellent biocompatibility and minimal cytotoxicity for AML-12 cells. Disulfide bond breakage of HES-SS-OA in the presence of H2O2 and GSH confirmed the redox sensitivity of the HES-SS-OA micelles and their excellent controlled release properties for OA. These findings suggest that HES-SS-OA can be potentially used in the future as a healthcare drug and medicine for the prevention or adjuvant treatment of inflammation.
摘要：
我们的研究旨在开发具有氧化还原敏感性和优异的控释性能的聚合物胶束。3,3'-二硫代二丙酸（DTDPA，合成聚合物的缩写：SS）作为ROS（活性氧）响应键和连接臂引入，以将羟乙基淀粉（HES）与齐墩果酸（OA）偶联，导致合成四种不同接枝率的HES-SS-OA。FTIR（傅立叶变换红外光谱）和1HNMR（1H核磁共振光谱）用于验证HES-SS-OA的成功组合。发现聚合物胶束以无定形形式包封OA，如XRD(X射线衍射)和DSC(差示扫描量热法)的结果所示。当OA在HES上的接枝率从7.72%提高到11.75%时,随着聚合物胶束由于增强的疏水性而变得致密，粒径从297.79nm减小到201.39nm。此外,zeta电位从-16.42mv变为-25.78mv，PDI(多分散指数)从0.3649下降到0.2435,临界胶束浓度(CMC)从0.0955mg/mL下降到0.0123mg/mL。红细胞溶血的结果，细胞毒性和细胞摄取表明HES-SS-OA对AML-12细胞具有优异的生物相容性和最小的细胞毒性。在H2O2和GSH存在下，HES-SS-OA的二硫键断裂证实了HES-SS-OA胶束的氧化还原敏感性及其对OA的优异控释性能。这些发现表明，HES-SS-OA将来可能用作预防或辅助治疗炎症的医疗保健药物和药物。
