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Nanomedicine (Lond). 2014 Jul;9(14):2109-21. doi: 10.2217/nnm.13.199. Epub 2014 Jan 28.

Pharmacokinetics and antitumor efficacy of paclitaxel-cyclodextrin complexes loaded in mucus-penetrating nanoparticles for oral administration.

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  • 1Department of Pharmacy & Pharmaceutical Technology, School of Pharmacy, University of Navarra, Calle de Irunlarrea, 1, 31080, Pamplona, Spain.

Abstract

AIM:

The authors report a novel approach for enhancing the oral absorption of paclitaxel (PTX) by encapsulation in poly(anhydride) nanoparticles (NPs) containing cyclodextrins and poly(ethylene glycol).

MATERIALS & METHODS:

Formulations were prepared using the solvent displacement method. Subsequently, pharmacokinetics and organ distribution assays were evaluated after oral administration into C57BL/6J mice. In addition, antitumor efficacy studies were performed in a subcutaneous tumor model of Lewis lung carcinoma.

RESULTS:

PTX-loaded NPs displayed sizes between 190-300 nm. Oral NPs achieved drug plasma levels for at least 24 h, with an oral bioavailability of 55-80%. Organ distribution studies revealed that PTX, orally administered in NPs, underwent a similar distribution to intravenous Taxol(®) (Bristol-Myers Squibb, NJ, USA). For in vivo antitumor assays, oral strategy maintained a slower tumor growth than intravenous Taxol.

CONCLUSION:

PTX orally administered in poly(anhydride) NPs, combined with cyclodextrins and poly(ethylene glycol), displayed sustained plasma levels and significant antitumor effect in a syngenic tumor model of carcinoma in mice.

KEYWORDS:

antitumor efficacy; cyclodextrin; nanoparticle; oral chemotherapy; paclitaxel; pharmacokinetics; poly(anhydride); poly(ethylene glycol) 2000

PMID:
24471503
[PubMed - in process]
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