In vitro investigation of ionic polysaccharide microspheres for simultaneous delivery of chemosensitizer and antineoplastic agent to multidrug-resistant cells
In vitro investigation of ionic polysaccharide microspheres for simultaneous delivery of chemosensitizer and antineoplastic agent to multidrug-resistant cells
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DOI：
10.1021/js9803353
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发表时间：
1999-04-01
影响因子：
3.8
通讯作者：
Bendayan, R
中科院分区：
文献类型：
--
作者：
Liu, Z;Wu, XY;Bendayan, R
瘤内药物浓度不足和多药耐药是导致实体瘤治疗失败的主要因素。通过微球同时递送化疗增敏和抗肿瘤药物可能会导致多药耐药（MDR）肿瘤的化疗增强。从右旋糖酐衍生的离子多糖微球被用来装载化学增敏剂（如维拉帕米）和抗癌药物如长春花碱。单药和双药的载药量都很高。平衡载药量取决于微球（MS）与药物的比例，以及在双药情况下药物与MS的相对亲和力。药物-MS的药物释放除了离子交换外，还包括MS的水化和肿胀。通过测量MDR细胞（CH(R)C5）对[H-3]长春花碱的摄取来评估ms递送的化学增敏剂在逆转耐药中的有效性。通过MS同时递送维拉帕米和长春花碱导致长春花碱摄取增加6-7倍，这一水平与使用游离药物溶液获得的摄取相似。结果表明，MS有效释放了抗肿瘤和化学增敏剂，并在此过程中保留了化学增敏剂的生物活性。
Insufficient intratumoral concentration of therapeutic agents and multidrug resistance are major factors responsible for failure of treatment of solid tumors. Simultaneous delivery of chemosensitizing and antineoplastic agents by microspheres could lead to enhanced chemotherapy of multidrug-resistant (MDR) tumors. Ionic polysaccharide microspheres derived from dextran were used to load chemosensitizers (e.g., verapamil) and anticancer drugs such as vinblastine. High drug loading was achieved for both a single agent and dual agents. The equilibrium drug loading was dependent on the ratio of the microspheres (MS) to the drug, as well as the relative affinity of the agents to the MS in the case of dual agents. The drug release from drug-MS involved hydration and swelling of the MS in addition to ion exchange. The effectiveness of MS-delivered chemosensitizers in the reversal of drug resistance was evaluated by measuring the uptake of [H-3]vinblastine by MDR cells (CH(R)C5). The concomitant delivery of verapamil with vinblastine by the MS led to a 6-7-fold increase in the uptake of vinblastine, a level similar to the uptake obtained with free drug solutions. The results suggest that the antineoplastic and chemosensitizing agents were released effectively from the MS and the bioactivity of the chemosensitizer was preserved during the process.