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It was the aim of this study to develop a nanoparticulate oral drug delivery system for leuprolide based on polyacrylic acid (PAA). In order to achieve formation of nanoparticles in a mild, aqueous environment, two different techniques were combined, namely hydrophobic ion pairing between leuprolide and sodium dodecyl sulphate in a first step, followed by encapsulation into nanoparticles gained by interpolymer complexation between polyacrylic acid and Pluronic F68. The obtained nanoparticles were characterized regarding particle size distribution, drug encapsulation efficiency and in vitro release profile. Additionally, the pharmacokinetic profiles of leuprolide after oral administration of PAA-nanoparticulate and PAA-control tablets to male Sprague-Dawley rats were assessed and compared. It could be shown, that hydrophobic ion pairing increased encapsulation efficacy of leuprolide and leads to a slowed drug release of nanoparticulate suspensions. Relative oral bioavailability of leuprolide could be increased by nanoparticulate tablets up to 4.2-fold. Results verify that the suggested approach is a promising strategy for the design of oral delivery systems for oral administration of peptide drugs.
Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 52c, Josef Möller Haus, 6020 Innsbruck, Austria.
This article was published in the following journal.
Name: Drug delivery
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Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.
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