Enhanced oral bioavailability of the hydrophobic chemopreventive agent (SR13668) in beagle dogs.

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 (100-200 nm) 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.
Authors	Aryamitra A Banerjee, Hao Shen, Mathew Hautman, Jaseem Anwer, Seungpyo Hong, Izet M Kapetanovic, Ying Liu, Alexander V Lyubimov
Journal	Current pharmaceutical biotechnology (Curr Pharm Biotechnol) Vol. 14 Issue 4 Pg. 464-9 ( 2013) ISSN: 1873-4316 [Electronic] Netherlands
PMID	23590143 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Carbazoles SR 13668 Suspensions Polylactic Acid-Polyglycolic Acid Copolymer Polyglycolic Acid Lactic Acid
Topics	Administration, Oral Animals Biological Availability Carbazoles (administration & dosage, chemistry, pharmacokinetics) Chemistry, Pharmaceutical (methods) Dogs Female Lactic Acid (administration & dosage, chemistry, pharmacokinetics) Male Nanoparticles (administration & dosage, chemistry) Particle Size Polyglycolic Acid (administration & dosage, chemistry, pharmacokinetics) Polylactic Acid-Polyglycolic Acid Copolymer Solubility Suspensions (administration & dosage, chemistry, pharmacokinetics)

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