کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1424737 986735 2011 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PEG-oligocholic acid telodendrimer micelles for the targeted delivery of doxorubicin to B-cell lymphoma
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
PEG-oligocholic acid telodendrimer micelles for the targeted delivery of doxorubicin to B-cell lymphoma
چکیده انگلیسی

Doxorubicin (DOX) is one of most common anti-cancer chemotherapeutic drugs, but its clinical use is associated with dose-limiting cardiotoxicity. We have recently developed a series of PEG-oligocholic acid based telodendrimers, which can efficiently encapsulate hydrophobic drugs and self-assemble to form stable micelles in aqueous condition. In the present study, two representative telodendrimers (PEG5k-CA8 and PEG2k-CA4) have been applied to prepare DOX micellar formulations for the targeted delivery of DOX to lymphoma. PEG2k-CA4 micelles, compared to PEG5k-CA8 micelles, were found to have higher DOX loading capacity (14.8% vs. 8.2%, w/w), superior stability in physiological condition, and more sustained release profile. Both of these DOX-loaded micelles can be efficiently internalized and release the drug in Raji lymphoma cells. DOX-loaded micelles were found to exhibit similar in vitro cytotoxic activities against both T- and B-lymphoma cells as the free DOX. The maximum tolerated dose (MTD) of DOX-loaded PEG2k-CA4 micelles in mice was approximately 15 mg/kg, which was 1.5-fold higher of the MTD of free DOX. Pharmacokinetics and biodistribution studies demonstrated that both DOX-loaded micelles were able to prolong the blood retention time, preferentially accumulate and penetrate in B-cell lymphomas via the enhanced permeability and retention (EPR) effect. Finally, DOX-PEG2k-CA4 micelles achieved enhanced anti-cancer efficacy and prolonged survival in Raji lymphoma bearing mice, compared to free DOX and PEGylated liposomal DOX (Doxil®) at the equivalent dose. In addition, the analysis of creatine kinase (CK) and lactate dehydrogenase (LDH) serum enzymes level indicated that DOX micellar formulations significantly reduced the cardiotoxicity associated with free DOX.

PEG2k-CA4 telodendrimer is able to efficiently encapsulate doxorubicin (DOX) to form stable micelles, which facilitate the targeted delivery of DOX to lymphoma, resulting in enhanced anti-cancer efficacy.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 155, Issue 2, 30 October 2011, Pages 272–281
نویسندگان
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