Jiangsu Jiankang Vocational College, Nanjing, Jiangsu, China.
Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA.
AAPS PharmSciTech. 2018 Feb;19(2):693-699. doi: 10.1208/s12249-017-0877-z. Epub 2017 Oct 2.
Paclitaxel (PTX) and gemcitabine (GEM) are often used in combination due to the synergistic anticancer effects. PTX and GEM combination showed a synergistic effect to SKOV-3 cells at a molar ratio of 1 to 1 and in PTX ➔ GEM sequence. Liposomes were explored as a carrier of PTX and GEM combination. We optimized the drug loading in liposomes varying the preparation method and co-encapsulated PTX and GEM in a single liposome preparation maintaining the maximum loading efficiency of each drug. However, drug release kinetics from the co-loaded liposomes (LpPG) was suboptimal because of the detrimental effect of PTX on GEM-release control. Instead, a mixture of LpP and LpG, which were separately optimized according to the desired release kinetics, achieved a greater cytotoxic effect than LpPG, due to the attenuation of GEM release relative to PTX. This study illustrates that co-encapsulation in a single carrier is not always desirable for the delivery of drug combinations, when the activity depends on the dosing sequence. These combinations may benefit from the mixed liposome approach, which offers greater flexibility in controlling the ratio and release kinetics of component drugs.
紫杉醇（PTX）和吉西他滨（GEM）经常联合使用，因为它们具有协同的抗癌作用。在摩尔比为 1:1 时，PTX 和 GEM 联合对 SKOV-3 细胞表现出协同作用，且 PTX➔GEM 顺序具有协同作用。脂质体被探索作为 PTX 和 GEM 联合的载体。我们通过改变制备方法来优化脂质体中的药物载量，并在单个脂质体制剂中共同包封 PTX 和 GEM，以保持每种药物的最大载药效率。然而，由于 PTX 对 GEM 释放控制的不利影响，从共载药脂质体（LpPG）中释放药物的动力学并不理想。相反，根据所需释放动力学分别优化的 LpP 和 LpG 的混合物比 LpPG 具有更大的细胞毒性作用，因为与 PTX 相比，GEM 的释放得到了抑制。本研究表明，当药物的活性取决于给药顺序时，对于药物联合的传递，将其共同包封在单个载体中并不总是理想的。这些组合可能受益于混合脂质体方法，该方法在控制药物成分的比例和释放动力学方面提供了更大的灵活性。
