Current Pharmaceutical Biotechnology

Zeno Foldes-Papp
Visiting Professor of Medical Biochemistry
HELIOS Clinical Center of Emergency Medicine
Department for Internal Medicine
Alte-Koelner-Strasse 9
D-51688 Koeln-Wipperfuerth
Germany

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Enhanced Oral Bioavailability of The Hydrophobic Chemopreventive Agent (Sr13668) in Beagle Dogs

Author(s): Aryamitra A. Banerjee, Hao Shen, Mathew Hautman, Jaseem Anwer, Seungpyo Hong, Izet M. Kapetanovic, Ying Liu and Alexander V. Lyubimov

Affiliation: Toxicology Research Laboratory, 808 S Wood St., Rm. 1306, University of Illinois at Chicago, Chicago, IL 60612, USA.

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.

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Article Details

VOLUME: 14
ISSUE: 4
Page: [464 - 469]
Pages: 6
DOI: 10.2174/1389201011314040012