Laser-responsive liposome for selective tumor targeting of nitazoxanide nanoparticles
Laser-responsive liposome for selective tumor targeting of nitazoxanide nanoparticles
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DOI：
10.1016/j.ejps.2017.10.038
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发表时间：
2018-01-01
影响因子：
4.6
通讯作者：
El-Kolaly, Mohamed T.
中科院分区：
文献类型：
--
作者：
Darwish, Wael M.;Bayoumi, Noha A.;El-Kolaly, Mohamed T.
硝唑尼特[2-（乙酰氧基）-N-（5-硝基-2-噻唑基）苯甲酰胺]，通常称为NTZ，是具有潜在抗癌反应性的抗寄生虫药物。然而，硝唑尼特的生物利用度是有限的，由于其较差的水溶性。在这项研究中，硝唑尼特可以成功地纳入一个稳定的生物相容性脂质体（NTZ-LP）使用改进的薄膜水合技术。此外，一种新的亲脂性酞菁星星聚合物R4 PcZn制备作为光敏剂和原位掺入脂质体制剂中的NTZ提供激光响应脂质体（NTZ-ZnPc-LP）。NTZ-LP和NTZ-ZnPc-LP均具有较高的包封率和体外释药速率。透射电子显微镜（TEM）图像和动态光散射（DLS）测量（NTZ-LP）和（NTZ-ZnPc-LP）显示单层囊泡的平均直径分别为192.2和87.4 nm。另外，以DMF和水为溶剂，通过膜挤出法制备了NTZ纳米粒。使用放射性标记的硝唑尼特I-125-NTZ类似地制备所有制剂。使用埃利希腹水癌在小鼠中诱导实体瘤后，将制备的制剂注射到小鼠的尾静脉中。用He-Ne激光（λ = 630 nm）照射注射（I-125-NTZ-ZnPc-LP）的动物的肿瘤部位。然后，用荧光标记法标记I-125-NTZ的生物分布。柜台结果表明，光响应制剂（I-125-NTZ-ZnPc-LP）在光照后肿瘤部位提供了较高的I-125 NTZ蓄积。这可归因于光敏化过程导致的脂质体脂质双层的破裂和由此产生的单线态氧。尽管（NTZ NPs）制剂显示NTZ在肿瘤中的快速积累，但其显示不利的快速血液清除率。
Nitazoxanide [2-(Acetyloxy)-N-(5-nitro-2-thiazolyl) benzamide], usually referred as NTZ, is an antiparasites drug with a potential anti-cancer reactivity. However, the bioavailability of nitazoxanide is limited due to its poor water solubility. In this study, nitazoxanide could be successfully incorporated in a stable biocompatible liposome (NTZ-LP) using a modified thin film hydration technique. Further, a novel lipophilic phthalocyanine star polymer R4PcZn was prepared as photosensitizer and in situ incorporated with NTZ in the liposome formulation affording a laser-responsive liposome (NTZ-ZnPc-LP). Both (NTZ-LP) and (NTZ-ZnPc-LP) showed high entrapment efficiency (EE) and high in vitro drug release rates. Transmission electron microscope (TEM) images and dynamic light scattering (DLS) measurements of (NTZ-LP) and (NTZ-ZnPc-LP) showed unilamellar vesicles of mean diameter 192.2 and 87.4 nm, respectively. In addition, NTZ nanoparticles (NTZ NPs) were prepared via membrane extrusion method using DMF and water as solvents. All formulations were similarly prepared using radiolabeled nitazoxanide I-125-NTZ. After induction of solid tumor in mices using Ehrlich Ascites Carcinoma, the prepared formulations were injected in the tail vein of the mices. Tumor sites of the animal injected with (I-125-NTZ-ZnPc-LP) were illuminated with a He-Ne laser (lambda = 630 nm). Afterwards, the biodistriburtion of I-125-NTZ was tagged using. counter. Results showed that the light-responsive formulation (I-125-NTZ-ZnPc-LP) affords a higher accumulation of I-125 NTZ in the tumor sites after illumination. This can be attributed to the rupture of liposome lipid bilayer as a result of the photosensitization process and the singlet oxygen species resulted thereof. Despite (NTZ NPs) formulation showed a rapid accumulation of NTZ in tumor, it showed unfavoured rapid blood clearance rate.