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| Content Provider | Springer Nature Link |
|---|---|
| Author | Narayan, Priyanka Liu, Garvey Kirtane, Ameya R. Panyam, Jayanth |
| Copyright Year | 2016 |
| Abstract | 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. |
| Starting Page | 65 |
| Ending Page | 73 |
| Page Count | 9 |
| File Format | |
| ISSN | 20935552 |
| Journal | Journal of Pharmaceutical Investigation |
| Volume Number | 47 |
| Issue Number | 1 |
| e-ISSN | 20936214 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2016-12-15 |
| Publisher Place | Dordrecht |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Polymer nanoparticles Biomedicine Multidrug resistance Oral drug delivery Bioavailability |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmaceutical Science |
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