کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5550700 1557298 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Distinct biodistribution of doxorubicin and the altered dispositions mediated by different liposomal formulations
ترجمه فارسی عنوان
توزیع بیولوژیکی متفاوتی از دوکسوروبیسین و اختلالات تغییر یافته بوسیله ترکیبات مختلف لیپوزوم
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
چکیده انگلیسی

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.

Driving force for tissue distribution of doxorubicin solution (blue), Doxil (red) and Myocet (green) was distinct among three formulations. The difference in doxorubicin tissue distribution may suggest different toxicity risk vs. benefit of different liposomal doxorubicin formulations.92

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 519, Issues 1–2, 15 March 2017, Pages 1-10
نویسندگان
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