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  • Title: Etoposide-incorporated tripalmitin nanoparticles with different surface charge: formulation, characterization, radiolabeling, and biodistribution studies.
    Author: Reddy LH, Sharma RK, Chuttani K, Mishra AK, Murthy RR.
    Journal: AAPS J; 2004 Oct 07; 6(3):e23. PubMed ID: 15760108.
    Abstract:
    Etoposide-incorporated tripalmitin nanoparticles with negative (ETN) and positive charge (ETP) were prepared by melt emulsification and high-pressure homogenization techniques. Spray drying of nanoparticles led to free flowing powder with excellent redispersibility. The nanoparticles were characterized by size analysis, zeta potential measurements, and scanning electron microscopy. The mean diameter of ETN and ETP nanoparticles was 391 nm and 362 nm, respectively, and the entrapment efficiency was more than 96%. Radiolabeling of etoposide and nanoparticles was performed with Technetium-99m (99mTc) with high labeling efficiency and in vitro stability. The determination of binding affinity of 99mTc-labeled complexes by diethylene triamine penta acetic acid (DTPA) and cysteine challenge test confirmed low transchelation of 99mTc-labeled complexes and high in vitro stability. Pharmacokinetic data of radiolabeled etoposide, ETN, and ETP nanoparticles in rats reveal that positively charged nanoparticles had high blood concentrations and prolonged blood residence time. Biodistribution studies of 99mTc-labeled complexes were performed after intravenous administration in mice. Both ETN and ETP nanoparticles showed significantly lower uptake by organs of the reticuloendothelial system such as liver and spleen (P < .001) compared with etoposide. The ETP nanoparticles showed a relatively high distribution to bone and brain (14-fold higher than etoposide and ETN at 4 hours postinjection) than ETN nanoparticles. The ETP nanoparticles with long circulating property could be a beneficial delivery system for targeting to tumors by Enhanced Permeability and Retention effect and to brain.
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