Formulation and characterization of oleic acid magnetic PEG PLGA nanoparticles for targeting glioblastoma multiforme

Abstract

Glioblastoma multiforme (GBM) is the most common and malignant form of astrocytoma with a median survival time of 1–2 years after diagnosis. The major treatment hurdle is the limited delivery of drugs to the brain due to the insurmountable blood brain barrier (BBB). Literature review reveals that nanoparticulate delivery system, in particular, magnetic polymeric nanoparticles in the presence of an external magnetic field may have enhanced permeation across the BBB. Therefore, the objective of this study was to fabricate the core of the polymeric nanoparticles with magnetic property. This core was fabricated by a modified seed synthesis method using tris(acetylacetonate) iron (III) [Fe(acac)3] as a precursor. To prevent the oxidation of Fe(acac)3, an overcoating with oleic acid was performed. The resulting oleic acid magnetic nanoparticle (OAMNP) was successfully prepared with a yield of 187.5 ± 4.2 mg. The particle size of the core was 9 ± 0.3 nm with a polydispersity index (PDI) of 0.189 ± 0.001. OAMNP was dispersed within the polymeric matrix comprising of poly(lactic acid)–methoxy poly(ethylene oxide) (PLA–PEG) and poly(lactic-co-glycolic acid) (PLGA) (PEG PLGA) by single emulsion solvent evaporation technique. The resulting nanoparticle had a particle size of 201 ± 2.1 nm with a PDI of 0.197 ± 0.003. The presence of co-polymer block linkage on the surface of OAMNP was qualitatively confirmed by proton NMR and FT-IR analysis. The mean entrapment efficiency of OAMNP within the PEG PLGA matrix was 43%. The iron concentration was 60 ± 3.1 µg/ml which was below is cytotoxic concentration, and in line with published literature. Furthermore, in the presence of an external magnetic field superior efficacy of OAMNP PEG PLGA NPS in U-138 cells was observed.