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Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma.

In a previous study, a formulation of methotrexate (MTX) incorporated in the lipid bilayer of 100-nm liposomes in the form of diglyceride ester (MTX-DG, lipophilic prodrug) was developed. In this study, first, the interactions of MTX-DG liposomes with various human and mouse tumor cell lines were st... Full description

Journal Title: International journal of nanomedicine 2017, Vol.12, pp.3735-3749
Main Author: Alekseeva, Anna A
Other Authors: Moiseeva, Ekaterina V , Onishchenko, Natalia R , Boldyrev, Ivan A , Singin, Alexander S , Budko, Andrey P , Shprakh, Zoya S , Molotkovsky, Julian G , Vodovozova, Elena L
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1178-2013 ; DOI: 10.2147/IJN.S133034
Link: http://search.proquest.com/docview/1903440147/?pq-origsite=primo
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recordid: proquest1903440147
title: Liposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma.
format: Article
creator:
  • Alekseeva, Anna A
  • Moiseeva, Ekaterina V
  • Onishchenko, Natalia R
  • Boldyrev, Ivan A
  • Singin, Alexander S
  • Budko, Andrey P
  • Shprakh, Zoya S
  • Molotkovsky, Julian G
  • Vodovozova, Elena L
subjects:
  • Animals–Administration & Dosage
  • Antimetabolites, Antineoplastic–Chemistry
  • Cell Line, Tumor–Chemistry
  • Cell Membrane–Drug Effects
  • Drug Delivery Systems–Drug Therapy
  • Female–Pathology
  • Humans–Chemistry
  • Injections, Intravenous–Administration & Dosage
  • Leukemia–Chemistry
  • Lipid Bilayers–Metabolism
  • Liposomes–Drug Therapy
  • Lymphoma, T-Cell–Pathology
  • Methotrexate–Administration & Dosage
  • Mice, Inbred C57bl–Chemistry
  • Mice, Inbred CBA–Administration & Dosage
  • Prodrugs–Chemistry
  • Antimetabolites, Antineoplastic
  • Lipid Bilayers
  • Liposomes
  • Prodrugs
  • Methotrexate
  • Endocytosis
  • Hematological Malignancies
  • Leukemia/Lymphoma
  • Lipophilic Prodrug
  • Liposomes
  • Methotrexate
ispartof: International journal of nanomedicine, 2017, Vol.12, pp.3735-3749
description: In a previous study, a formulation of methotrexate (MTX) incorporated in the lipid bilayer of 100-nm liposomes in the form of diglyceride ester (MTX-DG, lipophilic prodrug) was developed. In this study, first, the interactions of MTX-DG liposomes with various human and mouse tumor cell lines were studied using fluorescence techniques. The liposomes composed of egg phosphatidylcholine (PC)/yeast phosphatidylinositol/MTX-DG, 8:1:1 by mol, were labeled with fluorescent analogs of PC and MTX-DG. Carcinoma cells accumulated 5 times more MTX-DG liposomes than the empty liposomes. Studies on inhibitors of liposome uptake and processing by cells demonstrated that the formulation used multiple mechanisms to deliver the prodrug inside the cell. According to the data from the present study, undamaged liposomes fuse with the cell membrane only 1.5-2 hours after binding to the cell surface, and then, the components of liposomal bilayer enter the cell separately. The study on the time course of plasma concentration in mice showed that the area under the curve of MTX generated upon intravenous injection of MTX-DG liposomes exceeded that of intact MTX 2.5-fold. These data suggested the advantage of using liposomal formulation to treat systemic manifestation of hematological malignancies. Indeed, the administration of MTX-DG liposomes to recipient mice bearing T-cell leukemic lymphoma using a dose-sparing regimen resulted in lower toxicity and retarded lymphoma growth rate as compared with MTX. Keywords: liposomes, methotrexate, lipophilic prodrug, endocytosis, hematological malignancies, leukemia/lymphoma
language: eng
source:
identifier: E-ISSN: 1178-2013 ; DOI: 10.2147/IJN.S133034
fulltext: fulltext
issn:
  • 11782013
  • 1178-2013
url: Link


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titleLiposomal formulation of a methotrexate lipophilic prodrug: assessment in tumor cells and mouse T-cell leukemic lymphoma.
creatorAlekseeva, Anna A ; Moiseeva, Ekaterina V ; Onishchenko, Natalia R ; Boldyrev, Ivan A ; Singin, Alexander S ; Budko, Andrey P ; Shprakh, Zoya S ; Molotkovsky, Julian G ; Vodovozova, Elena L
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ispartofInternational journal of nanomedicine, 2017, Vol.12, pp.3735-3749
identifierE-ISSN: 1178-2013 ; DOI: 10.2147/IJN.S133034
subjectAnimals–Administration & Dosage ; Antimetabolites, Antineoplastic–Chemistry ; Cell Line, Tumor–Chemistry ; Cell Membrane–Drug Effects ; Drug Delivery Systems–Drug Therapy ; Female–Pathology ; Humans–Chemistry ; Injections, Intravenous–Administration & Dosage ; Leukemia–Chemistry ; Lipid Bilayers–Metabolism ; Liposomes–Drug Therapy ; Lymphoma, T-Cell–Pathology ; Methotrexate–Administration & Dosage ; Mice, Inbred C57bl–Chemistry ; Mice, Inbred CBA–Administration & Dosage ; Prodrugs–Chemistry ; Antimetabolites, Antineoplastic ; Lipid Bilayers ; Liposomes ; Prodrugs ; Methotrexate ; Endocytosis ; Hematological Malignancies ; Leukemia/Lymphoma ; Lipophilic Prodrug ; Liposomes ; Methotrexate
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descriptionIn a previous study, a formulation of methotrexate (MTX) incorporated in the lipid bilayer of 100-nm liposomes in the form of diglyceride ester (MTX-DG, lipophilic prodrug) was developed. In this study, first, the interactions of MTX-DG liposomes with various human and mouse tumor cell lines were studied using fluorescence techniques. The liposomes composed of egg phosphatidylcholine (PC)/yeast phosphatidylinositol/MTX-DG, 8:1:1 by mol, were labeled with fluorescent analogs of PC and MTX-DG. Carcinoma cells accumulated 5 times more MTX-DG liposomes than the empty liposomes. Studies on inhibitors of liposome uptake and processing by cells demonstrated that the formulation used multiple mechanisms to deliver the prodrug inside the cell. According to the data from the present study, undamaged liposomes fuse with the cell membrane only 1.5-2 hours after binding to the cell surface, and then, the components of liposomal bilayer enter the cell separately. The study on the time course of plasma concentration in mice showed that the area under the curve of MTX generated upon intravenous injection of MTX-DG liposomes exceeded that of intact MTX 2.5-fold. These data suggested the advantage of using liposomal formulation to treat systemic manifestation of hematological malignancies. Indeed, the administration of MTX-DG liposomes to recipient mice bearing T-cell leukemic lymphoma using a dose-sparing regimen resulted in lower toxicity and retarded lymphoma growth rate as compared with MTX. Keywords: liposomes, methotrexate, lipophilic prodrug, endocytosis, hematological malignancies, leukemia/lymphoma
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authorAlekseeva, Anna A ; Moiseeva, Ekaterina V ; Onishchenko, Natalia R ; Boldyrev, Ivan A ; Singin, Alexander S ; Budko, Andrey P ; Shprakh, Zoya S ; Molotkovsky, Julian G ; Vodovozova, Elena L
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