Gulzar Ahmad1, Florence Gattacecca2, Rana El Sadda3, Galina Botchkina3,4, Iwao Ojima3,5, James Egan6, Mansoor Amiji7. 1. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, 02115-5000, USA. 2. Institut de Recherche en Cancérologie de Montpellier IRCM, INSERM U1194, ICM, Université de Montpellier, Montpellier, France. 3. Institute of Chemical Biology and Drug Discovery, Stony Brook University, Stony Brook, New York, 11794-3400, USA. 4. Department of Pathology, School of Medicine, Stony Brook University, Stony Brook, New York, 11794-8691, USA. 5. Department of Chemistry, Stony Brook University, Stony Brook, New York, 11794-3400, USA. 6. Targagenix, Inc., 25 Health Sciences Drive, Stony Brook, New York, 11790-3382, USA. 7. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, 02115-5000, USA. m.amiji@northeastern.edu.
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.
PURPOSE: The main purpose of this study was to formulate an oil-in-water nanoemulsion of a next generation taxoidDHA-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-2humanprostate 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 mousetumor 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.
Entities:
Keywords:
biodistribution and pharmacokinetic; nanoemulsion formulation; prostate tumor; taxoid
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