Etoposide-incorporated tripalmitin nanoparticles with different surface charge: Formulation, characterization, radiolabeling, and biodistribution studies

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 ( 99m Tc) with high labeling efficiency and in vitro stability. The determination of binding affinity of 99m Tclabeled complexes by diethylene triamine penta acetic acid (DTPA) and cysteine challenge test confirmed low transchelation of 99m Tc-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 99m Tc-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.

Nanodrugs: pharmacokinetics and safety

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PLGA-Based Nanoparticles as Cancer Drug Delivery Systems

“…It is envisaged that intra-peritoneal delivery of etoposide through NPs would be a better approach for effectual treatment of peritoneal tumours. In this perspective, etoposide-loaded NPs were prepared applying nanoprecipitation and emulsionsolvent evaporation methods using PLGA in the presence of Pluronic F68 by Reddy et al The methods produced NPs with high entrapment efficiency of around 80% with continued release of the drug up to 48 hour (Acharya and Sahoo, 2011;Reddy et al, 2004).…”

A gamma scintigraphy study to investigate uterine targeting efficiency of raloxifene-loaded liposomes administered intravaginally in New Zealand white female rabbits

“…The radio colloids remains at bottom of the strip, while both the free pertechnetate and the labeled complex migrates with the solvent front. The activity moved with the solvent front using acetone was subtracted from that using pyridine:acetic acid:water as a mixture, the net % radiolabeled 99m Tc-RLH was calculated (Reddy et al, 2004).…”