title: Evaluating the potential of polymer nanoparticles for oral delivery of paclitaxel in drug-resistant cancer.
abstract: The present study was designed to explore the ability of polymeric nanoparticles to restore drug sensitivity to P-glycoprotein over-expressing cancer cells. A multidrug-resistant cell line 2780 AD and its sensitive parent cell line A2780 were studied in cell culture and as a xenografted tumour model. Paclitaxel was incorporated in poly(lactide-co-glycolide) nanoparticles of average diameter 125 nm stabilised by a positively charged surfactant. The nanoparticulate formulation was shown to be about sevenfold more potent than free paclitaxel against cell line A2780 and the poly(lactic-co-glycolic acid) (PLGA) nanoparticles alone were nontoxic to the cells at the concentrations required to deliver the drug. Whilst the oral formulation of paclitaxel was not as potent as the free drug in the A2780 xenografts, it showed significant activity against 2780 AD tumours, which are resistant to the maximum tolerated intravenous dose of paclitaxel. The efficacy of orally delivered paclitaxel in this drug-resistant model supports the concept of exploring nanoparticles for improved drug delivery.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, The John Arbuthnott Building, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR UK.
authors.forename: V
authors.initials: V
authors.lastname: Bhardwaj
authors.affiliation: The Centre for Oncology and Applied Pharmacology, Cancer Research UK, Department of Medical Oncology, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1BD UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Plumb
authors.affiliation: The Centre for Oncology and Applied Pharmacology, Cancer Research UK, Department of Medical Oncology, University of Glasgow, Garscube Estate, Switchback Road, Glasgow, G61 1BD UK.
authors.forename: J
authors.initials: J
authors.lastname: Cassidy
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, The John Arbuthnott Building, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR UK.
authors.forename: M N V
authors.initials: MN
authors.lastname: Ravi Kumar
keywords: EPR effect; Nanoparticles; Oral drug delivery; P-glycoprotein; Paclitaxel