Abstract
Potency and activity of SR13668 in cancer prevention have been proven in several in vitro and in vivo cancer models. However, the compound is highly hydrophobic and its limited oral bioavailability has hindered its clinical translation. In this study, we encapsulated SR13668 into polymeric nanoparticles to increase compound aqueous solubility and therefore bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (100-200nm) encapsulating SR13668 with narrow size distribution and high drug loading were generated by a continuous and scalable process of flash nanoprecipitation integrated with spray dry. A single gavage dose of SR13668-PLGA nanoparticles at 2.8 mg/kg was administered in eight beagle dogs. Drug levels in animal whole blood and plasma were measured over 24 hours. Enhanced bioavailability of SR13668 using nanoparticles compared with formulations of Labrasol® and neat drug in 0.5% methylcellulose is reported. This is the first attempt to study pharmacokinetics of SR13668 in large animals with orally administrated nanoparticle suspension.
Keywords: Polymeric nanoparticles, Bioavailability, Chemoprevention, Nanoprecipitation, Oral drug delivery, Pharmacokinetics, Size distribution, Surface charges.
Current Pharmaceutical Biotechnology
Title:Enhanced Oral Bioavailability of The Hydrophobic Chemopreventive Agent (Sr13668) in Beagle Dogs
Volume: 14 Issue: 4
Author(s): Aryamitra A. Banerjee, Hao Shen, Mathew Hautman, Jaseem Anwer, Seungpyo Hong, Izet M. Kapetanovic, Ying Liu and Alexander V. Lyubimov
Affiliation:
Keywords: Polymeric nanoparticles, Bioavailability, Chemoprevention, Nanoprecipitation, Oral drug delivery, Pharmacokinetics, Size distribution, Surface charges.
Abstract: Potency and activity of SR13668 in cancer prevention have been proven in several in vitro and in vivo cancer models. However, the compound is highly hydrophobic and its limited oral bioavailability has hindered its clinical translation. In this study, we encapsulated SR13668 into polymeric nanoparticles to increase compound aqueous solubility and therefore bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (100-200nm) encapsulating SR13668 with narrow size distribution and high drug loading were generated by a continuous and scalable process of flash nanoprecipitation integrated with spray dry. A single gavage dose of SR13668-PLGA nanoparticles at 2.8 mg/kg was administered in eight beagle dogs. Drug levels in animal whole blood and plasma were measured over 24 hours. Enhanced bioavailability of SR13668 using nanoparticles compared with formulations of Labrasol® and neat drug in 0.5% methylcellulose is reported. This is the first attempt to study pharmacokinetics of SR13668 in large animals with orally administrated nanoparticle suspension.
Export Options
About this article
Cite this article as:
Banerjee Aryamitra A., Shen Hao, Hautman Mathew, Anwer Jaseem, Hong Seungpyo, Kapetanovic Izet M., Liu Ying and Lyubimov Alexander V., Enhanced Oral Bioavailability of The Hydrophobic Chemopreventive Agent (Sr13668) in Beagle Dogs, Current Pharmaceutical Biotechnology 2013; 14 (4) . https://dx.doi.org/10.2174/1389201011314040012
DOI https://dx.doi.org/10.2174/1389201011314040012 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
An Updated Portrait of Pathogenesis, Molecular Markers and Signaling Pathways of Hepatocellular Carcinoma
Current Pharmaceutical Design MicroRNAs and Cancer; an Overview
Current Pharmaceutical Biotechnology Nummular Eczema: An Updated Review
Recent Patents on Inflammation & Allergy Drug Discovery Quantifying Glomerular Filtration Rates: Kidney Function Analysis Method and Apparatus
Recent Patents on Biomarkers Outcome Measures Following Sonodynamic Photodynamic Therapy – A Case Series
Current Drug Therapy Caveolin-1: A Promising Therapeutic Target for Diverse Diseases
Current Molecular Pharmacology Use of Radiopharmaceuticals for Diagnosis, Treatment, and Follow-Up of Differentiated Thyroid Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Silimarin and Cancer
Anti-Cancer Agents in Medicinal Chemistry Carbon Nanotubes in the Diagnosis and Treatment of Malignant Melanoma
Anti-Cancer Agents in Medicinal Chemistry Thapsigargin, Origin, Chemistry, Structure-Activity Relationships and Prodrug Development
Current Pharmaceutical Design Significance of Various Experimental Models and Assay Techniques in Cancer Diagnosis
Mini-Reviews in Medicinal Chemistry Melatonin in the Biliary Tract and Liver: Health Implications
Current Pharmaceutical Design Identification of Molecular Targets Associated with Ethanol Toxicity and Implications in Drug Development
Current Pharmaceutical Design Angiotensin II Receptor Blocker: Possibility of Antitumor Agent for Prostate Cancer
Mini-Reviews in Medicinal Chemistry Telomeric Repeat Containing RNA (TERRA): Aging and Cancer
CNS & Neurological Disorders - Drug Targets The Activity of Titanocene T Against Xenografted Caki-1 Tumors
Letters in Drug Design & Discovery Alcohol and the Cardiovascular System: A Double-Edged Sword
Current Pharmaceutical Design Sanguinarine: A Double-Edged Sword of Anticancer and Carcinogenesis and Its Future Application Prospect
Anti-Cancer Agents in Medicinal Chemistry Cannabis Phenolics and their Bioactivities
Current Medicinal Chemistry Long-Term Immunovirogical Effect and Tolerability of a Maraviroc- Containing Regimen in Routine Clinical Practice
Current HIV Research