Liu Z, Cheung R, Wu X Y, Ballinger J R, Bendayan R, Rauth A M
Faculty of Pharmacy, University of Toronto, ON, M5S 2S2, Toronto, Canada.
J Control Release. 2001 Dec 13;77(3):213-24. doi: 10.1016/s0168-3659(01)00473-4.
The objective of this study was to investigate various factors that influence doxorubicin (Dox) loading onto and release from sulfopropyl dextran ion-exchange microspheres (MS), and to evaluate the anticancer activity of the released drug in vitro. Dox was incorporated into the MS by incubating the MS with aqueous solutions of Dox at room temperature. The drug release was carried out at 37 degrees C in aqueous solutions containing NaCl with or without CaCl2. The kinetics of drug absorption and release, the amount of Dox released, and the stability of Dox after loading, freeze-drying, and release were determined by spectrophotometry. The cytotoxicity of Dox (the original drug or that released from MS) against murine EMT6 breast cancer cells was assessed using a clonogenic assay. An increase in the MS to drug ratio resulted in a higher absorption rate and a higher fraction of the drug extracted from the solution. The release rate and the equilibrium fraction of Dox released increased with a decrease in the initial amount of Dox loaded or an increase in the salt concentration. The addition of divalent ions (Ca2+) promoted drug release compared to NaCl alone. The percent loss of colony forming ability of the cells, a measure of cytotoxicity of the released Dox, was the same as parent Dox solutions, indicating that the drug bioactivity was fully preserved after the drug loading and release cycle. This work demonstrated that various drug release rates were achieved by varying the drug loading and that the MS-delivered Dox was effective against the cancer cells in vitro.
本研究的目的是探究影响阿霉素（Dox）负载到磺丙基葡聚糖离子交换微球（MS）上以及从该微球释放的各种因素，并评估释放药物的体外抗癌活性。通过在室温下将微球与阿霉素水溶液孵育，将阿霉素载入微球。药物释放是在含或不含氯化钙的氯化钠水溶液中于37℃进行的。通过分光光度法测定药物吸收和释放的动力学、阿霉素释放量以及负载、冻干和释放后阿霉素的稳定性。使用克隆形成试验评估阿霉素（原始药物或从微球释放的药物）对小鼠EMT6乳腺癌细胞的细胞毒性。微球与药物比例的增加导致更高的吸收率和从溶液中提取的更高药物比例。阿霉素的释放速率和平衡释放分数随着负载的阿霉素初始量的减少或盐浓度的增加而增加。与单独的氯化钠相比，二价离子（Ca2+）的添加促进了药物释放。细胞集落形成能力的丧失百分比，作为释放的阿霉素细胞毒性的一种度量，与原始阿霉素溶液相同，表明在药物负载和释放循环后药物生物活性得到了充分保留。这项工作表明，通过改变药物负载可以实现不同的药物释放速率，并且微球递送的阿霉素在体外对癌细胞有效。
