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负载依托泊苷的纳米颗粒在荷道尔顿淋巴瘤肿瘤小鼠体内的肿瘤摄取、生物分布及药代动力学增强

Enhanced tumor uptake, biodistribution and pharmacokinetics of etoposide loaded nanoparticles in Dalton's lymphoma tumor bearing mice.

作者信息

Snehalatha Movva, Kolachina Venugopal, Saha Ranendra Narayan, Babbar Anil Kumar, Sharma Navneet, Sharma Rakesh Kumar

机构信息

Department of Pharmaceutics, Birla Institute of Technology and Science, Pilani, Rajasthan, India.

出版信息

J Pharm Bioallied Sci. 2013 Oct;5(4):290-7. doi: 10.4103/0975-7406.120081.

Abstract

BACKGROUND

Nanotechnology plays a remarkable role in the field of the treatment of Lymphomas associated with tumor.

OBJECTIVE

The purpose of this study is to determine and to compare the tumor uptake, biodistribution and pharmacokinetics of radiolabeled etoposide and etoposide loaded nanoparticles in Dalton's Lymphoma tumor bearing mice and healthy mice.

MATERIALS AND METHODS

Etoposide loaded nanoparticles were prepared by nanoprecipitation technique using the poly (lactic-co-glycolic) acid (PLGA) in the presence of Pluronic F 68 (F 68) as a stabilizer and characterized by particle size analyzer, zeta potential and transmission electron microscope. Etoposide and etoposide loaded nanoparticles were labeled with Technetium-99m (Tc-99m) by the direct method and various quality control tests were carried out. The labeling parameters like labeling efficiency, stability, etc., were optimized to get high labeling efficiency as well as stability of the labeled formulations. Tc-99m labeled formulations were administered intravenously in Balb C mice and their biodistribution and pharmacokinetics were determined.

RESULTS

Mean size of the etoposide loaded PLGA nanoparticles was found to be 105.1 nm. The concentration of both free etoposide and nanoparticles increased with time and showed higher tumor concentrations of both free etoposide and nanoparticles increased with time and showed higher retention, indicating their applicability in effective and prolonged tumor therapy. Nuclear scintigraphic images confirm the presence of labeled complexes at the site of tumor for 24 h at higher concentration than in the normal muscles.

CONCLUSION

This study indicated higher tumor affinity and targeting properties of etoposide loaded nanoparticles than free etoposide.

摘要

背景

纳米技术在与肿瘤相关的淋巴瘤治疗领域发挥着显著作用。

目的

本研究的目的是测定并比较放射性标记的依托泊苷和负载依托泊苷的纳米颗粒在荷道尔顿淋巴瘤肿瘤小鼠和健康小鼠体内的肿瘤摄取、生物分布及药代动力学。

材料与方法

采用纳米沉淀技术,以聚乳酸-羟基乙酸共聚物(PLGA)为载体,泊洛沙姆F68(F68)为稳定剂制备负载依托泊苷的纳米颗粒,并用粒度分析仪、ζ电位仪和透射电子显微镜对其进行表征。依托泊苷和负载依托泊苷的纳米颗粒采用直接法用99m锝(Tc-99m)进行标记,并进行各种质量控制测试。对标记效率、稳定性等标记参数进行优化,以获得高标记效率以及标记制剂的稳定性。将Tc-99m标记的制剂静脉注射到Balb C小鼠体内,测定其生物分布和药代动力学。

结果

负载依托泊苷的PLGA纳米颗粒的平均粒径为105.1 nm。游离依托泊苷和纳米颗粒的浓度均随时间增加,且游离依托泊苷和纳米颗粒在肿瘤中的浓度均随时间增加并显示出更高的滞留率,表明它们在有效的长期肿瘤治疗中的适用性。核闪烁图像证实标记复合物在肿瘤部位存在24小时,其浓度高于正常肌肉。

结论

本研究表明,负载依托泊苷的纳米颗粒比游离依托泊苷具有更高的肿瘤亲和力和靶向特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c082/3831742/d5f82e734671/JPBS-5-290-g004.jpg

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