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Title of Journal: Pharm Res

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Abbravation: Pharmaceutical Research

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Springer US

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DOI

10.1006/inco.1996.0018

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1573-904X

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Preclinical Studies of Pegylated and NonPegylate

Authors: P Chastagner H Sudour J Mriouah M BarberiHeyob V BernierChastagner S Pinel
Publish Date: 2014/07/22
Volume: 32, Issue: 1, Pages: 158-166
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Abstract

Free doxorubicin DXR is not currently used to treat brain tumors because i the blood–brain barrier limits the drug deposition into the brain ii lethal toxic effects occur when combined with radiation therapy Since encapsulation of DXR within liposomal carriers could overcome these drawbacks the present study aimed at evaluating the radiosensitizing properties of nonpegylated NPLDXR and pegylated PLDXR liposomal doxorubicin on orthotopic highgrade glioma xenografts U87We showed that encapsulation of DXR ensured a preferential deposition of DXR in tumoral tissue in comparison with normal brain tissue the best AUC tumor tissue/AUC normal tissue ratio depended greatly on the schedule Overall thanks to the optimization of the delivery schedule we demonstrated a radiosensitizing effect for both liposomal DXR without toxicity of this combination on the U87 human malignant glioma orthotopic xenograftsThis study shows that the use of nanocarriers allowing targeting of intracerebral tumor renders relevant the combination of anthracyclin with radiation therapy to treat brain tumors opening a new field of therapeutic applications However our results point out that for each new delivery system the administration schedules need to be rigorously optimized

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