载有紫杉醇的氧化还原敏感混合胶束的制备及评价

对纳米胶束聚合物载体进行结构修饰,不仅可以使难溶药物增溶,还可以使载药载体在肿瘤组织聚集。本文以紫杉醇(PTX)为模型药物,合成了以二硫键(-S-S-)和油酸(OA)修饰后的聚乙二醇1 000维生素E琥珀酸酯(TPGS)与脱氧胆酸钠(NADC)按不同摩尔比制成混合胶束,并合成了以硫醚键修饰的TPGS与NADC混合胶束进行对比研究。主要考察了修饰后聚合物的临界胶束浓度(CMC)值,TPGS-OA与NADC不同摩尔比对胶束的理化性质的影响,对比二硫键和硫醚键氧化还原敏感释药的能力。结果表明,当TPGS-OA与NADC的摩尔比减小,载药量增加,但稳定性降低;当摩尔比为3∶1时,TPGS-S-S-OA/NADC混合胶束的粒径、电位和包封率分别为96.24±2.42 nm、-24.4 mV和(98.7±0.08)%,混合胶束的溶血率在2%以下;二硫键修饰的混合胶束中PTX在10 mmol·L^-1H₂O₂介质(pH 7.4)5 h内释放96%,其与硫醚键修饰后的释药能力相当,但在低pH值(pH 5.5)介质中胶束的稳定性降低。所有动...

Preparation and evaluation of redox sensitive mixed micelles containing paclitaxel

The structural modification of nano-micellar polymer carriers can not only increase the solubiliza‐tion of insoluble drugs,but also make drug-loaded carriers aggregate in tumor tissues.In this paper,paclitaxel(PTX)was used as a model drug,D-α-tocopherol polyethyleneglycol 1000 succinate(TPGS)modified by disulfide bond(-S-S-)and oleic acid(OA)was synthesized and mixed micelles were prepared with different molar ratios of sodium deoxycholate(NADC),and TPGS and NADC mixed micelles modified by thioether bond were synthesized for comparative study.The effects of the critical micelle concentration(CMC)of the modified polymer and the molar ratio of TPGS-OA and NADC on the physical and chemical properties of the micelle were investigated Finally,the redox drug release ability of disulfide bond and thioether bond was compared.The results showed that when the molar ratio of TPGS-OA to NADC decreased,the drug loading increased,but the stability decreased When the molar ratio was 3∶1,the particle size,potential and entrapment efficiency of TPGS-S-S-OA/NADC were96.24±0.14 nm,-24.4 mV and(98.7±0.08)%,respectively,hemolysis rate of mixed micelles is less than 2%.The disulfide modified mixed micelles released PTX completely within 5 h in 10 mmol·L^-1H2O2environment(pH 7.4)which was similar to that of thioether modified micelles.It was also found that the stability of micelles decreased when the pH value was low.All animal experiments were in accordance with ethical standards and were approved by the Animal Experimental Center of Shenyang Pharmaceutical University(No.211002300032403).In this study we mainly developed stable nano-micelle carriers which can target drug release in tumor heterogeneous environment.