Pharmaceutical Research

, 35:91 | Cite as

Biodistribution and Pharmacokinetic Evaluations of a Novel Taxoid DHA-SBT-1214 in an Oil-in-Water Nanoemulsion Formulation in Naïve and Tumor-Bearing Mice

  • Gulzar Ahmad
  • Florence Gattacecca
  • Rana El Sadda
  • Galina Botchkina
  • Iwao Ojima
  • James Egan
  • Mansoor Amiji
Research Paper
  • 93 Downloads

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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 words

biodistribution and pharmacokinetic nanoemulsion formulation prostate tumor taxoid 

Abbreviations

AUC

Area under curve

CL

Clearance

CSCs

Cancer Stem Cells

DHA

Docosahexaenoic acid

DSPE-PEG2000

1, 2-distearoyl-Sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000]

HPLC

High Performance Liquid Chromatography

IACUC

Institutional Animal Care and Use Committee

LAL

Limulus Amebocyte Lysate

LOD

Limit of Detection

LOQ

Limit of Quantification

MDR

Multi Drug Resistance

MRT

Mean residence time

MSCGM

Mesenchymal Stem Cell Growth Media

PEG

Poly Ethylene Glycol

PDI

Polydispersity index

PrC

Prostate cancer

PTX

Paclitaxel

SLS

Sodium Lauryl Sulfate

t1/2

Terminal half-life

TEM

Transmission Electron Microscopy

TFA

Trifluoroacetic acid

TICs

Tumor Initiating Cells

Vss

Volume of distribution at steady state

Notes

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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Gulzar Ahmad
    • 1
  • Florence Gattacecca
    • 2
  • Rana El Sadda
    • 3
  • Galina Botchkina
    • 3
    • 4
  • Iwao Ojima
    • 3
    • 5
  • James Egan
    • 6
  • Mansoor Amiji
    • 1
  1. 1.Department of Pharmaceutical Sciences, School of PharmacyNortheastern UniversityBostonUSA
  2. 2.Institut de Recherche en Cancérologie de Montpellier IRCM, INSERM U1194, ICMUniversité de MontpellierMontpellierFrance
  3. 3.Institute of Chemical Biology and Drug DiscoveryStony Brook UniversityStony BrookUSA
  4. 4.Department of Pathology, School of MedicineStony Brook UniversityStony BrookUSA
  5. 5.Department of ChemistryStony Brook UniversityStony BrookUSA
  6. 6.Targagenix, Inc.Stony BrookUSA

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