Biodistribution and bioimaging studies of hybrid paclitaxel nanocrystals: lessons learned of the EPR effect and image-guided drug delivery.
Biodistribution and bioimaging studies of hybrid paclitaxel nanocrystals: lessons learned of the EPR effect and image-guided drug delivery.
复制标题
DOI：
10.1016/j.jconrel.2013.06.039
复制
发表时间：
2013-11-28
期刊：
影响因子：
--
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Hollis CP;Weiss HL;Leggas M;Evers BM;Gemeinhart RA;Li T
通过从溶液中结晶制备紫杉醇（PTX）纳米晶体（200 nm）。通过在人HT-29结肠癌异种移植鼠模型中的存活研究来检查抗肿瘤功效和毒性。紫杉醇治疗的抗肿瘤活性与常规增溶制剂（Taxol®）相当，但如存活研究的结果所示，产生较低的毒性。氚标记的PTX纳米晶体进一步用物理上整合在晶格中的近红外（NIR）荧光染料产生。氚标记的PTX纳米晶体的生物分布和肿瘤蓄积在静脉内给药后立即测定，并通过闪烁计数长达48小时。同时进行动物的全身光学成像;还从切除的肿瘤和安乐死动物的主要器官测量荧光强度。发现肿瘤中的药物蓄积小于20 mg/kg静脉注射剂量的1%。氚标记微粒法和光学成像法测定的生物分布存在定性相关性，但存在定量差异。不同的结果提出了改进用于癌症治疗和诊断的混合纳米晶体设计的可能方法。该研究还提出了增强渗透性和保留（EPR）效应在肿瘤靶向中的一般作用以及生物成像（特别是混合纳米晶体）在跟踪药物分布和药代动力学方面的有效性的问题。
Paclitaxel (PTX) nanocrystals (200 nm) were produced by crystallization from solution. Antitumor efficacy and toxicity were examined through a survival study in a human HT-29 colon cancer xenograft murine model. The antitumor activity of the nanocrystal treatments was comparable with that by the conventional solubilization formulation (Taxol®), but yielded less toxicity as indicated by the result of survival study. Tritium-labeled PTX nanocrystals were further produced with a near infrared (NIR) fluorescent dye physically integrated in the crystal lattice. Biodistribution and tumor accumulation of the tritium-labeled PTX nanocrystals were determined immediately after intravenous administration and up to 48 hours by scintillation counting. Whole-body optical imaging of animals was concurrently carried out; fluorescent intensities were also measured from excised tumors and major organs of euthanized animals. It was found that drug accumulation in the tumor was less than 1% of 20 mg/kg intravenous dose. Qualitatively correlation was identified between the biodistribution determined by using tritium-labeled particles and that using optical imaging, but quantitative divergence existed. The divergent results suggest possible ways to improve the design of hybrid nanocrystals for cancer therapy and diagnosis. The study also raises questions of the general role of the enhanced permeability and retention (EPR) effect in tumor targeting and the effectiveness of bioimaging, specifically for hybrid nanocrystals, in tracking drug distribution and pharmacokinetics.
登录
查看更多内容
DOI：
10.3181/0808-mr-250
发表时间：
2009-02
期刊：
Experimental biology and medicine (Maywood, N.J.)
影响因子：
--
作者：
Blanco E;Kessinger CW;Sumer BD;Gao J
通讯作者：
Gao J
DOI：
10.1016/0167-5699(91)90009-i
发表时间：
1991-09-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
FRANK, MM;FRIES, LF
通讯作者：
FRIES, LF
影响因子：
3
作者：
EISEMAN, JL;EDDINGTON, ND;EGORIN, MJ
通讯作者：
EGORIN, MJ
影响因子：
29.4
作者：
Barbé, C;Bartlett, J;Calleja, G
通讯作者：
Calleja, G
影响因子：
10.8
作者：
Lee, Beom Suk;Park, Kyeongsoon;Kim, Sang Yoon
通讯作者：
Kim, Sang Yoon