Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 101, Issue 5, Pages 1319-1327Publisher
WILEY
DOI: 10.1002/jbm.a.34442
Keywords
etoposide; nanoparticles; PLGA; Poloxamer 188; brain tumor
Funding
- La Ligue Contre le Cancer [2007.10.0640]
- Region Champagne Ardenne
- DRRT Champagne Ardenne (MESR)
- EU-program FEDER
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Etoposide (VP-16) is a hydrophobic anticancer agent inhibiting Topoisomerase II, commonly used in pediatric brain chemotherapeutic schemes as mildly toxic. Unfortunately, despite its appropriate solubilization in vehicle solvents, its poor bioavailability and limited passage of the bloodbrain barrier concur to disappointing results requiring the development of new delivery system forms. In this study, etoposide formulated as a parenteral injectable solution (Teva (R)) was loaded into all-biocompatible poly(lactide-co-glycolide) (PLGA) or PLGA/P188-blended nanoparticles (size 110130 nm) using a fully biocompatible nanoprecipitation technique. The presence of coprecipitated P188 on encapsulation efficacies and in vitro drug release was investigated. Drug encapsulation was determined using HPLC. Inflammatory response was checked by FACS analysis on human monocytes. Cytotoxic activity of the various simple (Teva (R)) or double (Teva (R)-loaded NPs) formulations was studied on the murine C6 and F98 cell lines. Obtained results suggest that, although noninflammatory neither nontoxic by themselves, the use of PLGA and PLGA/P188 nanoencapsulations over pre-existing etoposide formulation could induce a greatly improved cytotoxic activity. This approach demonstrated a promising perspective for parenteral delivery of VP16 and potential development of a therapeutic entity. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
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