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
Keywords: Polymeric nanoparticles, Bioavailability, Chemoprevention, Nanoprecipitation, Oral drug delivery, Pharmacokinetics,
Size distribution, Surface charges.
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