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.
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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 |
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