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KMID : 0369820170470010065
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Jorunal of Korean Pharmaceutical Sciences
2017 Volume.47 No. 1 p.65 ~ p.73
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Polymer-surfactant nanoparticles for improving oral bioavailability of doxorubicin
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Kirtane Ameya R.
Narayan Priyanka
Liu Garvey
Panyam Jayanth
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Abstract
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The oral bioavailability of several clinically relevant drugs is compromised because of their limited absorption across the gastrointestinal tract. Active efflux of the drug by transporters such as P-glycoprotein (P-gp) present on the luminal side of the intestinal epithelial cells limits drug absorption. Encapsulation of drugs in nanoparticles can reduce transporter-mediated efflux and increase drug absorption. The purpose of this manuscript is to determine if the bioavailability of doxorubicin, a P-gp substrate, could be increased by encapsulation in nanoparticles. We synthesized polymer-surfactant nanoparticles comprised of a sodium alginate core complexed with doxorubicin and stabilized by the surfactant Aerosol OT (AOT). Encapsulation of doxorubicin in nanoparticles improved its transport across cell monolayers as evidenced by Transwell® studies. Drug uptake studies were carried out in cells overexpressing P-gp and those with basal levels of P-gp. These studies revealed that AOT inhibited P-gp activity and improved drug uptake in P-gp expressing cells by ~5-6-fold. Increase in drug uptake was found only in cells expressing P-gp and was limited to P-gp substrates. We also determined the in vivo oral bioavailability of the nanoparticle formulation of doxorubicin in mice. Doxorubicin delivered in the form of nanoparticles had a higher bioavailability relative to that with the free drug. This study shows that the oral bioavailability of P-gp substrates such as doxorubicin can be enhanced by delivering them in AOT-alginate nanoparticles.
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KEYWORD
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Oral drug delivery, Polymer nanoparticles, Multidrug resistance, Bioavailability
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