Etoposide encapsulation in surface-modified poly(lactide-co-glycolide) nanoparticles strongly enhances glioma antitumor efficiency.
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 blood-brain barrier concur to disappointing results requiring the development of new delivery system forms. In this study, etoposide formulated as a parenteral injectable solution (Teva®) was loaded into all-biocompatible poly(lactide-co-glycolide) (PLGA) or PLGA/P188-blended nanoparticles (size 110-130 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®) or double (Teva®-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.
Pharmaceutical Sciences Department, Institut de Chimie Moléculaire de Reims (ICMR UMR CNRS 7213), School of Pharmacy, 51095 Reims Cedex, France.
Maïté
M
Callewaert
Sylvain
S
Dukic
Laurence
L
Van Gulick
Mélanie
M
Vittier
Valérie
V
Gafa
Marie-Christine
MC
Andry
Michaël
M
Molinari
V Gaëlle
VG
Roullin
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D005047:Etoposide / Q000008:administration & dosage* / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry* / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005047:Etoposide