Without internal affiliation

  • Author: Zucker, Daniel

    Unknown

  • Author: Andriyanov, Alexander V.

    The Hebrew University-Hadassah Medical School (IL), Department of Biochemistry and Molecular Biology, IMRIC

  • Author: Steiner, Ariel

    The Hebrew University of Jerusalem (IL), The Institute of Chemistry

  • Author: Raviv, Uri

    The Hebrew University of Jerusalem (IL), The Institute of Chemistry

  • Author: Barenholz, Yechezkel

    The Hebrew University-Hadassah Medical School (IL), Department of Biochemistry and Molecular Biology, IMRIC

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Recently, developing drug delivery systems exhibiting controlled drug release at the tumor sites emerged as an attractive option for enhancing anticancer therapeutic efficacy. It seems, however, unlikely that single agent therapies will prove effective enough against the myriad cells present within the malignancy. Therefore, next generation nanotherapeutics must not only find their way to the solid tumor but also must effectively destroy the diverse populations of cells promoting tumor growth. Nanoliposomes offer an important advantage in the delivery of a combination of drugs acting synergistically in cancer treatment. They allow controlling the pharmacokinetics and biodistribution of the drugs by uniform time and spatial co-delivery of the agents. However, successful translation of such complex formulations into the clinic relies on understanding critical physicochemical characteristics. These include: liposomes’ membrane phase and dynamics, size distribution, state of encapsulated drug, internal environment of liposome, state of grafted polyethylene glycol at the liposome surface, and in-vivo drug release rate. They determine the pharmacokinetics of the formulation and the bioavailability of the drugs. We encapsulated the combination of vincristine (VCR) and topotecan (TPT) in the same nanoliposome (LipoViTo). Our in-vitro and in-vivo characterization of LipoViTo provides an explanation for the good therapeutic efficacy that was previously reported by us. Moreover,we have described how to study these critical features for a two-drug in one nanoliposome formulation. This characterization is an important step for a rational clinical development and for how to ensure liposome product quality of LipoViTo and other liposomal formulations alike. © 2011 Elsevier B.V. All rights reserved.
Original languageEnglish
JournalJournal of Controlled Release
Publication date2011
ISSN0168-3659
DOIs
StatePublished
CitationsWeb of Science® Times Cited: 12
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