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Tytuł pozycji:

Preparation of parenteral nanocrystal suspensions of etoposide from the excipient free dry state of the drug to enhance in vivo antitumoral properties.

Tytuł:
Preparation of parenteral nanocrystal suspensions of etoposide from the excipient free dry state of the drug to enhance in vivo antitumoral properties.
Autorzy:
Martin B; Université de Paris, CNRS, Inserm, UTCBS, Chemical and Biological Technologies for Health Group (utcbs.cnrs.fr), Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006, Paris, France.; Department of Neurological Surgery, Weill Medical College of Cornell University, New York, NY, USA.
Seguin J; Université de Paris, CNRS, Inserm, UTCBS, Chemical and Biological Technologies for Health Group (utcbs.cnrs.fr), Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006, Paris, France.
Annereau M; Gustave Roussy, 114 rue Edouard Vaillant, 94800, PharmacyVillejuif, France.
Fleury T; Gustave Roussy, 114 rue Edouard Vaillant, 94800, PharmacyVillejuif, France.
Lai-Kuen R; Université de Paris, CNRS, Inserm, Cellular and Molecular Imaging Technology Platform, Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006, Paris, France.
Neri G; Université de Paris, CNRS, Inserm, UTCBS, Chemical and Biological Technologies for Health Group (utcbs.cnrs.fr), Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006, Paris, France.
Lam A; Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada.
Bally M; Department of Experimental Therapeutics, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Mignet N; Université de Paris, CNRS, Inserm, UTCBS, Chemical and Biological Technologies for Health Group (utcbs.cnrs.fr), Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006, Paris, France.
Corvis Y; Université de Paris, CNRS, Inserm, UTCBS, Chemical and Biological Technologies for Health Group (utcbs.cnrs.fr), Faculté de Pharmacie, 4 Avenue de l'Observatoire, 75006, Paris, France. .
Źródło:
Scientific reports [Sci Rep] 2020 Oct 22; Vol. 10 (1), pp. 18059. Date of Electronic Publication: 2020 Oct 22.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: London : Nature Publishing Group, copyright 2011-
MeSH Terms:
Nanoparticles*
Nanotechnology*
Antineoplastic Agents/*pharmacokinetics
Antineoplastic Agents/*pharmacology
Drug Compounding/*methods
Etoposide/*pharmacokinetics
Etoposide/*pharmacology
Neoplasms/*drug therapy
Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Biological Availability ; Cell Line, Tumor ; Disease Models, Animal ; Dosage Forms ; Etoposide/administration & dosage ; Etoposide/adverse effects ; Mice ; Suspensions
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Substance Nomenclature:
0 (Antineoplastic Agents)
0 (Dosage Forms)
0 (Suspensions)
6PLQ3CP4P3 (Etoposide)
Entry Date(s):
Date Created: 20201023 Date Completed: 20210322 Latest Revision: 20210322
Update Code:
20240105
PubMed Central ID:
PMC7581827
DOI:
10.1038/s41598-020-74809-z
PMID:
33093456
Czasopismo naukowe
Nanoparticle technology in cancer chemotherapy is a promising approach to enhance active ingredient pharmacology and pharmacodynamics. Indeed, drug nanoparticles display various assets such as extended blood lifespan, high drug loading and reduced cytotoxicity leading to better drug compliance. In this context, organic nanocrystal suspensions for pharmaceutical use have been developed in the past ten years. Nanocrystals offer new possibilities by combining the nanoformulation features with the properties of solid dispersed therapeutic ingredients including (i) high loading of the active ingredient, (ii) its bioavailability improvement, and (iii) reduced drug systemic cytotoxicity. However, surprisingly, no antitumoral drug has been marketed as a nanocrystal suspension until now. Etoposide, which is largely used as an anti-cancerous agent against testicular, ovarian, small cell lung, colon and breast cancer in its liquid dosage form, has been selected to develop injectable nanocrystal suspensions designed to be transferred to the clinic. The aim of the present work is to provide optimized formulations for nanostructured etoposide solutions and validate by means of in vitro and in vivo evaluations the efficiency of this multiphase system. Indeed, the etoposide formulated as a nanosuspension by a bottom-up approach showed higher blood life span, reduced tumor growth and higher tolerance in a murine carcinoma cancer model. The results obtained are promising for future clinical evaluation of these etoposide nanosuspensions.

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