Distinct biodistribution of doxorubicin and the altered dispositions mediated by different liposomal formulations

被引：51

作者：

Luo, Ruijuan ^{[1
]}

Li, Yan ^{[2
]}

He, Miao ^{[1
]}

Zhang, Huixia ^{[1
]}

Yuan, Hebao ^{[1
]}

Johnson, Mark ^{[1
]}

Palmisano, Maria ^{[2
]}

Zhou, Simon ^{[2
]}

Sun, Duxin ^{[1
]}

机构：

[1] Univ Michigan, Dept Pharmaceut Sci, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA

[2] Celgene Corp, Translat Dev & Clin Pharmacol, 86 Morris Ave, Summit, NJ 07920 USA

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2017年 / 519卷 / 1-2期

关键词：

Liposome; Doxorubicin; Tissue distribution; Drug delivery; METASTATIC BREAST-CANCER; PROLONGED CIRCULATION TIME; CONVENTIONAL DOXORUBICIN; PHASE-I/II; MACROMOLECULAR THERAPEUTICS; ENCAPSULATED DOXORUBICIN; REDUCED CARDIOTOXICITY; 1ST-LINE TREATMENT; ANTITUMOR-ACTIVITY; DELIVERY-SYSTEMS;

D O I：

10.1016/j.ijpharm.2017.01.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The liposomal formulations of doxorubicin produced distinct efficacy and toxicity profiles compared to doxorubicin solution in cancer patients. This study aims to investigate the drug tissue distribution and the driving force for tissue distribution from doxorubicin solution and two liposomal delivery systems, Doxil and Myocet. These three formulations were intravenously administered to mice at a single dose of 5 mg/kg. Eleven organs, plasma and blood were collected at different time points. Total doxorubicin concentrations in each specimen were measured with LC MS/MS. Compared to doxorubicin solution, both Doxil and Myocet produced distinct doxorubicin tissue exposure in all 11 tissues. Interestingly, the tissue exposure by Myocet was drastically different from that of Doxil and showed a formulation dependent pattern. Cmax of doxorubicin in heart tissue by Doxil and Myocet was approximately 60% and 50% respectively of that by doxorubicin solution. The predominant driving force for doxorubicin tissue distribution is liposomal-doxorubicin deposition for Doxil and free drug concentration for doxorubicin solution. For Myocet, the driving force for tissue distribution is predominately liposomal-doxorubicin deposition into tissues within the first 4 h; as the non-PEGylated doxorubicin liposomal decomposes, the driving force for tissue distribution is gradually switched to the released free doxorubicin. Unique tissue distributions are correlated with their toxicity profiles. (C) 2017 Elsevier B.V. All rights reserved.

引用

页码：1 / 10

页数：10

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