JOURNAL OF CONTROLLED RELEASE | 卷:229 |
DAFODIL: A novel liposome-encapsulated synergistic combination of doxorubicin and 5FU for low dose chemotherapy | |
Article | |
Camacho, Kathryn M.1  Menegatti, Stefano2  Vogus, Douglas R.1  Pusuluri, Anusha1  Fuchs, Zoe1  Jarvis, Maria1  Zakrewsky, Michael1  Evans, Michael A.1  Chen, Renwei1  Mitragotri, Samir1  | |
[1] Univ Calif Santa Barbara, Ctr Bioengn, Dept Chem Engn, Santa Barbara, CA 93106 USA | |
[2] N Carolina State Univ, BTEC, Dept Biomed Engn, Dept Chem & Biomol Engn, Raleigh, NC 27695 USA | |
关键词: Drug combinations; Synergistic; Chemotherapy; Liposomes; Nanoparticles; | |
DOI : 10.1016/j.jconrel.2016.03.027 | |
来源: Elsevier | |
【 摘 要 】
PEGylated liposomes have transformed chemotherapeutic use of doxorubicin by reducing its cardiotoxicity; however, it remains unclear whether liposomal doxorubicin is therapeutically superior to free doxorubicin. Here, we demonstrate a novel PEGylated liposome system, named DAFODIL (Doxorubicin And 5-Flurouracil Optimally Delivered In a Liposome) that inarguably offers superior therapeutic efficacies compared to free drug administrations. Delivery of synergistic ratios of this drug pair led to greater than 90% reduction in tumor growth of murine 4T1 mammary carcinoma in vivo. By exploiting synergistic ratios, the effect was achieved at remarkably low doses, far below the maximum tolerable drug doses. Our approach re-invents the use of liposomes for multidrug delivery by providing a chemotherapy vehicle which can both reduce toxicity and improve therapeutic efficacy. This methodology is made feasible by the extension of the ammonium-sulfate gradient encapsulation method to nucleobase analogues, a liposomal entrapment method once conceived useful only for anthracyclines. Therefore, our strategy can be utilized to efficiently evaluate various chemotherapy combinations in an effort to translate more effective combinations into the clinic. (C) 2016 Elsevier B.V. All rights reserved.
【 授权许可】
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