Proapoptotic lipid nanovesicles: Synergism with paclitaxel in human lung adenocarcinoma A549 cells

被引:22
作者
Joshi, Nitin [1 ]
Shanmugam, Thanigaivel [1 ]
Kaviratna, Anubhav [1 ]
Banerjee, Rinti [1 ]
机构
[1] Indian Inst Technol, Dept Biosci & Bioengn, WRCBB, Bombay 400067, Maharashtra, India
关键词
Lung cancer; Proapoptotic lipid nanovesicles; Paclitaxel; Phosphatidylserine; Aerosol; Combination chemotherapy; PHOSPHATIDYLSERINE INDUCES APOPTOSIS; DRUG-DELIVERY; LIPOSOMES; RECOGNITION; MACROPHAGES; DYSFUNCTION; INHIBITION; MECHANISMS; CASPASES; TAXOL;
D O I
10.1016/j.jconrel.2011.07.025
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The present study focuses on the development and evaluation of phosphatidylserine based proapoptotic lipid nanovesicles (PSN-PTX) as aerosols for synergistic activity with paclitaxel against lung cancer. PSN-PTX showed a unimodal size distribution of the particles (100-200 nm), negative surface charge of -29 mV and high encapsulation efficiency of paclitaxel (82%) with 19% of it releasing in 48 h. PSN-PTX was found to be highly surface active as compared to Taxol (R), marketed formulation of paclitaxel, whose surface activity was found to be detrimental for pulmonary mechanics. PSN-PTX also showed high airway patency in capillary surfactometer unlike Taxol (R), suggesting its ability to mimic pulmonary surfactant functions. High deposition of PSN-PTX in lower impingement chamber of twin impinger upon nebulization suggested it to be capable of reaching the terminal regions of the lungs. Nanovesicles showed facilitated and ATP dependent active uptake by A549 cells. The combination of phosphatidylserine nanovesicles and paclitaxel as PSN-PTX enhanced cytotoxicity in A549 cell line showing an IC50 of 18 nM which is 10-50 folds less than the IC50 values observed for blank phosphtidylserine nanovesicles and paclitaxel alone. Further, the combination index was found to be less than one which indicates a synergism of the two components. DNA fragmentation study showed that blank phosphatidylserine nanovesicles induce apoptosis in A549 cells and hence behave as proapoptotic nanovesicles in the combination therapy. Overall, these studies suggest the therapeutic potential and advantages of combination chemotherapy of proapoptotic lipid nanovesicles with encapsulated paclitaxel and their feasibility for aerosol administration in the treatment of lung cancer. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:413 / 420
页数:8
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