A New Approach to Reduce Toxicities and to Improve Bioavailabilities of Platinum-Containing Anti-Cancer Nanodrugs

被引：56

作者：

Liu, Li ^{[1
]}

Ye, Qing ^{[1
]}

Lu, Maggie ^{[2
]}

Lo, Ya-Chin ^{[2
]}

Hsu, Yuan-Hung ^{[2
]}

Wei, Ming-Cheng ^{[2
]}

Chen, Yu-Hsiang ^{[3
]}

Lo, Shen-Chuan ^{[3
]}

Wang, Shian-Jy ^{[3
]}

Bain, Daniel J. ^{[4
]}

Ho, Chien ^{[1
]}

机构：

[1] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA

[2] Ind Technol Res Inst, Biomed Technol & Device Res Labs, Hsinchu, Taiwan

[3] Ind Technol Res Inst, Mat & Chem Res Labs, Hsinchu, Taiwan

[4] Univ Pittsburgh, Dept Geol & Planetary Sci, Pittsburgh, PA 15260 USA

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

基金：

美国安德鲁·梅隆基金会; 美国国家卫生研究院;

关键词：

DRUG-DELIVERY; CISPLATIN NEPHROTOXICITY; OXALIPLATIN; NANOPARTICLES; CLEARANCE; SYSTEM; TUMORS; LIVER;

D O I：

10.1038/srep10881

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Platinum (Pt) drugs are the most potent and commonly used anti-cancer chemotherapeutics. Nanoformulation of Pt drugs has the potential to improve the delivery to tumors and reduce toxic side effects. A major challenge for translating nanodrugs to clinical settings is their rapid clearance by the reticuloendothelial system (RES), hence increasing toxicities on off-target organs and reducing efficacy. We are reporting that an FDA approved parenteral nutrition source, Intralipid 20%, can help this problem. A dichloro (1, 2-diaminocyclohexane) platinum (II)-loaded and hyaluronic acid polymercoated nanoparticle (DACHPt/HANP) is used in this study. A single dose of Intralipid (2 g/kg, clinical dosage) is administrated [intravenously (i.v.), clinical route] one hour before i.v. injection of DACHPt/HANP. This treatment can significantly reduce the toxicities of DACHPt/HANP in liver, spleen, and, interestingly, kidney. Intralipid can decrease Pt accumulation in the liver, spleen, and kidney by 20.4%, 42.5%, and 31.2% at 24-hr post nanodrug administration, respectively. The bioavailability of DACHPt/HANP increases by 18.7% and 9.4% during the first 5 and 24 hr, respectively.

引用

页数：11

共 43 条

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