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Development and in vivo evaluation of an oral drug delivery system for paclitaxel

Paper ID Volume ID Publish Year Pages File Format Full-Text
8412 589 2011 6 PDF Available
Title
Development and in vivo evaluation of an oral drug delivery system for paclitaxel
Abstract

The aim of the present study was to investigate the effect of poly(acrylic acid)-cysteine (PAA-cysteine) exhibiting a molecular mass of 100 and 250 kDa and reduced glutathione (GSH) on the absorption of the P-glycoprotein (P-gp) and cytochrome P450 (CYP450) substrate paclitaxel in vitro and in vivo. In vitro transport studies were performed with Caco-2 monolayers. Furthermore, the delivery system based on PAA-cysteine, GSH and paclitaxel was evaluated in vivo in rats. In vitro, the formulation comprising 0.5% (m/v) PAA-cysteine (100 kDa)/0.5% (m/v) GSH improved the transport of paclitaxel 6.7-fold (Papp = 8.7 ± 1.3 × 10−6 cm/s) in comparison to paclitaxel itself serving as buffer only control (Papp = 1.3 ± 0.4 × 10−6 cm/s). Moreover, in the presence of the formulation containing 0.5% (m/v) PAA-cysteine (250 kDa)/0.5% (m/v) GSH paclitaxel absorption was even 7.4-fold (Papp = 9.7 ± 0.3 × 10−6 cm/s) improved in comparison to the buffer only control. In vivo, the oral administration of formulations containing 1 mg of paclitaxel, 1 mg of GSH and 8 mg of PAA-cysteine (100 kDa or 250 kDa) resulted in an improved paclitaxel plasma concentration and bioavailability. The area under the plasma concentration-time curve (AUC0–8) of paclitaxel was 4.7-fold and 5.7-fold improved in comparison to the oral formulation containing paclitaxel alone, respectively. Moreover, cmax was improved by 6.3-fold and even 7.3-fold in comparison to the oral formulation containing paclitaxel alone, respectively. Thus, according to the achieved results it is suggested that PAA-cysteine in combination with GSH would be a potentially valuable tool for improving the oral bioavailability of P-gp and CYP450 substrates such as paclitaxel.

Keywords
Thiomers; Poly(acrylic acid)-cysteine; Paclitaxel; P-Glycoprotein; Cytochrome P450; Oral drug delivery
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Development and in vivo evaluation of an oral drug delivery system for paclitaxel
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 1, January 2011, Pages 170–175
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us