DAFODIL: A novel liposome-encapsulated synergistic combination of doxorubicin and 5FU for low dose chemotherapy

TitleDAFODIL: A novel liposome-encapsulated synergistic combination of doxorubicin and 5FU for low dose chemotherapy
Publication TypeJournal Article
Year of Publication2016
AuthorsCamacho KM, Menegatti S, Vogus DR, Pusuluri A, Fuchs Z, Jarvis M, Zakrewsky M, Evans MA, Chen R, Mitragotri S
JournalJournal of Controlled Release
Volume229
Pagination154 - 162
ISSN0168-3659
KeywordsNanoparticles
Abstract

Abstract \{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 multi-drug 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.

URLhttp://www.sciencedirect.com/science/article/pii/S0168365916301602
DOI10.1016/j.jconrel.2016.03.027