Etoposide encapsulation in surface‐modified poly(lactide‐co‐glycolide) nanoparticles strongly enhances glioma antitumor efficiency

Abstract

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.

Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells

“…Concerning ETO-loaded nanoparticles prepared in the last decade, only very high dimensioned pegylated liposomal ETO nanoparticles of 491 nm, characterized by a limited DL% of 10%, proved to have a very high entrapment efficiency of 99% [76]. In other cases, the ETO EE% was either very low (4-14%) [77] or, though high (75-84%) [78], were not as high as the EE% achieved in this study by using dendrimer 4. Only recently, Thiyagarajan et al [79], have prepared a series of polymeric nanoparticles containing ETO for targeting cancer cells that had a high DL% (62-90%) and in some cases very high EE% (49-94%).…”

Development and Evaluation of Sustained-Release Etoposide-Loaded Poly(ε-Caprolactone) Implants

“…Considering the favorable results obtained for the etoposide-loaded PCL implants, new studies may be performed to verify the possibility to employ the devices in the treatment of ocular tumors (such as retinoblastoma) and brain cancers (such as malignant glioma). The low bioavailability of the drug into the site of disease may be the major reason for the failure of systemic chemotherapy of retinoblastoma and brain tumors (53)(54)(55). Thus, in the case of treatment of retinoblastoma, etoposide-loaded PCL implants can be inserted into the vitreous cavity, promoting drug release directly at the target site.…”

Cover Picture: A New Class of Tunable Heterojunction by using Two Support Materials for the Synthesis of Supported Bimetallic Catalysts (ChemCatChem 2/2015)

“…The Ru II ‐complex‐loaded NPs were prepared by using a modified nanoprecipitation method50 derived from Fessi and co‐workers 51, 37. Briefly, PLGA (50 mg, 1 % w/v) and P188 (6 mg, 1 % w/v) were co‐dissolved in glycofurol (5 mL) in the presence of Ru complex (5×10 −11 mol).…”