Etoposide-incorporated tripalmitin nanoparticles with different surface charge: Formulation, characterization, radiolabeling, and biodistribution studies
Journal Title: The AAPS Journal - Year 2004, Vol 6, Issue 3
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 of99mTc-labeled complexes by diethylene triamine penta acetic acid (DTPA) and cysteine challenge test confirmed low transchelation of99mTc-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 of99mTc-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.
Authors and Affiliations
Lakkireddy Harivardhan Reddy, Rakesh Kumar Sharma, Krishna Chuttani, Anil Kumar Mishra, Rayasa Ramachandra Murthy
Keywords
Related Articles
- EP ID EP681929
- DOI 10.1208/aapsj060323
- Views 78
- Downloads 0
Curcumin and Cancer Cells: How Many Ways Can Curry Kill Tumor Cells Selectively?
Cancer is a hyperproliferative disorder that is usually treated by chemotherapeutic agents that are toxic not only to tumor cells but also to normal cells, so these agents produce major side effects. In addition, these a...
Pharmacokinetics and Tissue Disposition of Lenalidomide in Mice
Lenalidomide is a synthetic derivative of thalidomide exhibiting multiple immunomodulatory activities beneficial in the treatment of several hematological malignancies. Murine pharmacokinetic characterization necessary f...
The Utility of Modeling and Simulation Approaches to Evaluate Immunogenicity Effect on the Therapeutic Protein Pharmacokinetics
While therapeutic proteins (TP), particularly recombinant human proteins and fully human monoclonal antibodies, are designed to have a low immunogenic potential in humans, a clinical immune response does sometimes occur...
Modeling Subpopulations with the $MIXTURE Subroutine in NONMEM: Finding the Individual Probability of Belonging to a Subpopulation for the Use in Model Analysis and Improved Decision Making
In nonlinear mixed effects modeling using NONMEM, mixture models can be used for multimodal distributions of parameters. The fraction of individuals belonging to each of the subpopulations can be estimated, and the most...
Stereoselective pharmacokinetics of ifosfamide in male and female rats
The stereoselective pharmacokinetics of ifosfamide (IF) were investigated in male and female Sprague-Dawley rats. Following intravenous administration of IF deuterium-labeled pseudoracemates into rats at 40 mg/kg, IF ena...