Biodistribution and Pharmacokinetic Evaluations of a Novel Taxoid DHA-SBT-1214 in an Oil-in-Water Nanoemulsion Formulation in Naïve and Tumor-Bearing Mice
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The main purpose of this study was to formulate an oil-in-water nanoemulsion of a next generation taxoid DHA-SBT-1214 and evaluate its biodistribution and pharmacokinetics.
DHA-SBT-1214 was encapsulated in a fish oil containing nanoemulsion using a high pressure homogenization method. Following morphological characterization of the nanoemulsions, qualitative and quantitative biodistribution was evaluated in naïve and cancer stem cell-enriched PPT-2 human prostate tumor bearing mice.
DHA-SBT-1214 was successfully encapsulated up to 20 mg/ml in the nanoemulsion formulation and had an average oil droplet size of 200 nm. Using a DiR near infra-red dye encapsulated nanoemulsion, we have shown the delivery of nanoemulsion to mouse tumor region. By quantitative analysis, DHA-SBT-1214 encapsulated nanoemulsion demonstrated improved pharmacokinetic properties in plasma and different tissues as compared to its solution form. Furthermore, the nanoemulsions were stable and had slower in vitro drug release compared to its solution form.
The results from this study demonstrated effective encapsulation of the drug in a nanoemulsion and this nanoemulsion showed sustained plasma levels and enhanced tumor delivery relative to the solution form.
Key wordsbiodistribution and pharmacokinetic nanoemulsion formulation prostate tumor taxoid
Area under curve
Cancer Stem Cells
1, 2-distearoyl-Sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000]
High Performance Liquid Chromatography
Institutional Animal Care and Use Committee
Limulus Amebocyte Lysate
Limit of Detection
Limit of Quantification
Multi Drug Resistance
Mean residence time
Mesenchymal Stem Cell Growth Media
Poly Ethylene Glycol
Sodium Lauryl Sulfate
Transmission Electron Microscopy
Tumor Initiating Cells
Volume of distribution at steady state
Acknowledgments and Disclosures
Financial support was provided by the National Cancer Institute of the National Institutes of Health through grants and contract R21-CA150085 (to GB), R01-CA103314 and R44-CA132396 (to IO), HHSN261201500018C (to JE) and U01-CA151452 and R21-CA179652 (to MA). Additionally, transmission electron microscopy of the nanoemulsion samples was performed by Mr. William Fowle at the Electron Microscopy Center, Northeastern University (Boston, MA).
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