title: 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.forename: Aryamitra A
authors.initials: AA
authors.lastname: Banerjee
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.forename: Mathew
authors.initials: M
authors.lastname: Hautman
authors.forename: Jaseem
authors.initials: J
authors.lastname: Anwer
authors.forename: Seungpyo
authors.initials: S
authors.lastname: Hong
authors.forename: Izet M
authors.initials: IM
authors.lastname: Kapetanovic
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Toxicology Research Laboratory, 808 S Wood St., Rm. 1306, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Lyubimov
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004285:Dogs; D005260:Female; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013535:Suspensions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D002227:Carbazoles; C523402:SR 13668; D013535:Suspensions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid