Polyelectrolyte nanoparticles with high drug loading enhance the oral uptake of hydrophobic compounds

W P Cheng, A I Gray, L Tetley, T L B Hang, A G Schatzlein, I F Uchegbu

    Research output: Contribution to journalArticlepeer-review

    59 Citations (Scopus)

    Abstract

    In the pharmaceutical industry, orally active compounds are required to have sufficient water solubility to enable dissolution within the gastrointestinal tract prior to absorption. Limited dissolution within the gastrointestinal tract often reduces the bioavailability of hydrophobic drugs. To improve gastrointestinal tract dissolution, nonaqueous solvents are often used in the form of emulsions and microemulsions. Here, we show that oil-free polyelectrolyte nanosystems (micellar dispersions and 100 - 300 nm particles) prepared from poly(ethylenimines) derivatized with cetyl chains and quaternary ammonium groups are able to encapsulate high levels of hydrophobic drug (0.20 g of drug per g of polymer) for over 9 months, as demonstrated using cyclosporine A (log P = 4.3). The polyelectrolytes facilitate the absorption of hydrophobic drugs within the gastrointestinal tract by promoting drug dissolution and by a hypothesized mechanism involving paracellular drug transport. Polyelectrolyte nanoparticle drug blood levels are similar to those obtained with commercial microemulsion formulations. The polyelectrolytes do not promote absorption by inhibition of the P-glycoprotein efflux pump.

    Original languageEnglish
    Pages (from-to)1509-1520
    Number of pages12
    JournalBiomacromolecules
    Volume7
    Issue number5
    DOIs
    Publication statusPublished - May 2006

    Keywords

    • CYCLOSPORINE-A
    • CACO-2 CELLS
    • TRANSEPITHELIAL PERMEABILITY
    • NONIONIC SURFACTANTS
    • P-GLYCOPROTEIN
    • MICELLES
    • ABSORPTION
    • COPOLYMERS
    • CYTOCHROME-P450
    • SOLUBILIZATION

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