Hepatocellular carcinoma (HCC) is a cancer with high incidence and mortality rates worldwide. In the various treatment methods for HCC, the lack of cancer cell specificity and the development of multidrug resistance (...Hepatocellular carcinoma (HCC) is a cancer with high incidence and mortality rates worldwide. In the various treatment methods for HCC, the lack of cancer cell specificity and the development of multidrug resistance (MDR) are two major obstacles in the treatment of HCC. P-glycoprotein (P-gp) is an ATP-dependent drug efflux pump that can reduce the accumulation of drugs in cells and make cancer cells acquire drug resistance. D-α-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) can inhibit the activity of ATP-dependent P-gp and serves as an effective excipient for overcoming tumor multidrug resistance (MDR). TPGS has been approved by the FDA as a safe adjuvant and is widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its application in drug delivery, such as high biocompatibility, enhanced drug solubility, improved drug permeation, and selective antitumor activity. In recent years, more and more studies have found that using TPGS-modified nanomaterials to load chemotherapy drugs to treat tumors can effectively reverse the drug resistance of tumors, including HCC. This review summarizes and discusses the role of TPGS in reversing tumor drug resistance and the therapeutic effects of TPGS-based drugs on drug-resistant HCC.展开更多
为延长盐酸吉西他滨(1)的半衰期、提高生物利用度,采用逆相蒸发法制备聚乙二醇1000维生素E琥珀酸酯(TPGS)修饰的1脂质体(1-LP),并考察其性质和在大鼠体内的药动学行为。结果表明,所得1-LP的粒径为(212.6±7.2)nm、z电位为(-31.1...为延长盐酸吉西他滨(1)的半衰期、提高生物利用度,采用逆相蒸发法制备聚乙二醇1000维生素E琥珀酸酯(TPGS)修饰的1脂质体(1-LP),并考察其性质和在大鼠体内的药动学行为。结果表明,所得1-LP的粒径为(212.6±7.2)nm、z电位为(-31.1±2.9)m V、包封率为(70.56±1.92)%、载药量为(7.41±0.05)%。绘制了1-LP和1水溶液在p H 7.4磷酸盐缓冲液中的体外释药曲线,并用几种常用模型拟合试验数据。结果二者的释药数据均用双指数模型拟合效果较好(R^2为0.996和0.947)。对比研究了SD大鼠尾静脉注射给予1-LP或市售1注射液后的药动学行为。血浆中的药物浓度采用HPLC法测定。所得主要药动学参数为:t_(1/2)(4.12±0.73)和(1.32±0.10)h,AUC_(0→∞)(37.57±1.09)和(9.64±0.20)mg·L·h^(-1),MRT_(0→∞)(6.06±0.28)和(1.67±0.04)h。展开更多
文摘Hepatocellular carcinoma (HCC) is a cancer with high incidence and mortality rates worldwide. In the various treatment methods for HCC, the lack of cancer cell specificity and the development of multidrug resistance (MDR) are two major obstacles in the treatment of HCC. P-glycoprotein (P-gp) is an ATP-dependent drug efflux pump that can reduce the accumulation of drugs in cells and make cancer cells acquire drug resistance. D-α-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) can inhibit the activity of ATP-dependent P-gp and serves as an effective excipient for overcoming tumor multidrug resistance (MDR). TPGS has been approved by the FDA as a safe adjuvant and is widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its application in drug delivery, such as high biocompatibility, enhanced drug solubility, improved drug permeation, and selective antitumor activity. In recent years, more and more studies have found that using TPGS-modified nanomaterials to load chemotherapy drugs to treat tumors can effectively reverse the drug resistance of tumors, including HCC. This review summarizes and discusses the role of TPGS in reversing tumor drug resistance and the therapeutic effects of TPGS-based drugs on drug-resistant HCC.
文摘为延长盐酸吉西他滨(1)的半衰期、提高生物利用度,采用逆相蒸发法制备聚乙二醇1000维生素E琥珀酸酯(TPGS)修饰的1脂质体(1-LP),并考察其性质和在大鼠体内的药动学行为。结果表明,所得1-LP的粒径为(212.6±7.2)nm、z电位为(-31.1±2.9)m V、包封率为(70.56±1.92)%、载药量为(7.41±0.05)%。绘制了1-LP和1水溶液在p H 7.4磷酸盐缓冲液中的体外释药曲线,并用几种常用模型拟合试验数据。结果二者的释药数据均用双指数模型拟合效果较好(R^2为0.996和0.947)。对比研究了SD大鼠尾静脉注射给予1-LP或市售1注射液后的药动学行为。血浆中的药物浓度采用HPLC法测定。所得主要药动学参数为:t_(1/2)(4.12±0.73)和(1.32±0.10)h,AUC_(0→∞)(37.57±1.09)和(9.64±0.20)mg·L·h^(-1),MRT_(0→∞)(6.06±0.28)和(1.67±0.04)h。
