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  • The performance of PEGylated nanocapsules of perfluorooctyl bromide as an ultrasound contrast agent.

The performance of PEGylated nanocapsules of perfluorooctyl bromide as an ultrasound contrast agent.

Biomaterials (2009-12-02)
Raquel Díaz-López, Nicolas Tsapis, Mathieu Santin, Sharon Lori Bridal, Valérie Nicolas, Danielle Jaillard, Danielle Libong, Pierre Chaminade, Véronique Marsaud, Christine Vauthier, Elias Fattal
ABSTRACT

The surface of polymeric nanocapsules used as ultrasound contrast agents (UCAs) was modified with PEGylated phospholipids in order to escape recognition and clearance by the mononuclear phagocyte system and achieve passive tumor targeting. Nanocapsules consisted of a shell of poly(lactide-co-glycolide) (PLGA) encapsulating a liquid core of perfluorooctyl bromide (PFOB). They were decorated with poly(ethylene glycol-2000)-grafted distearoylphosphatidylethanolamine (DSPE-PEG) incorporated in the organic phase before the solvent emulsification-evaporation process. The influence of DSPE-PEG concentration on nanocapsule size, surface charge, morphology, hydrophobicity and complement activation was evaluated. Zeta potential measurements, Hydrophobic interaction chromatography and complement activation provide evidence of DSPE-PEG presence at nanocapsule surface. Electronic microscopy reveals that the core/shell structure is preserved up to 2.64 mg of DSPE-PEG for 100 mg PLGA. In vivo ultrasound imaging was performed in mice bearing xenograft tumor with MIA PaCa-2 cells, either after an intra-tumoral or intravenous injection of nanocapsules. Tumor was observed only after the intra-tumoral injection. Despite the absence of echogenic signal in the tumor after intravenous injection of nanocapsules, histological analysis reveals their accumulation within the tumor tissue demonstrating that tissue distribution is not the unique property required for ultrasound contrast agents to be efficient.

MATERIALS
Product Number
Brand
Product Description

Millipore
Millex® PVDF syringe filter, pore size 0.45 μm, diam. 4 mm, sterile, hydrophilic
Sigma-Aldrich
1-Bromoheptadecafluorooctane, 99%