Etoposide-incorporated Tripalmitin Nanoparticles With Different Surface Charge: Formulation, Characterization, Radiolabeling, and Biodistribution Studies

Etoposide-incorporated Tripalmitin Nanoparticles With Different Surface Charge: Formulation, Characterization, Radiolabeling, and Biodistribution Studies
October 2004
Lakkireddy Harivardhan Reddy, Rakesh Kumar Sharma, Krishna Chuttani, Anil Kumar Mishra, and Rayasa Ramachandra Murthy
The AAPS Journal 2004; 6 (3) Article 23
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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 99mTclabeled 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.