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In vitro evaluation of glycol chitosan based formulations as oral delivery systems for efflux pump inhibition.

Recently, we have reported that glycol chitosan (GCS) was able to reverse the P- glycoprotein (P-gp) efflux pump. The objective of the present study was to evaluate the potential of two GCS-based dosage forms (aqueous solution or nanoparticle suspension) for oral administration of the P-gp substrate Rho-123. A further aim of the present study was to assess the effect of the glycol chitosan-4-thiobutylamidine thiomer (GCS-TBA) on P-gp activity considering that the corresponding thiomer of chitosan series is a well-known P-gp inhibitor. Pre-treatment of Caco-2 cell monolayer with a GCS solution or GCS-based nanoparticles increased the absorptive transport of Rho-123 across the monolayer of 1.43-fold. The modification of GCS with 2-iminothiolane led to GCS-TBA conjugate which did not show any P-gp inhibitory activity. Therefore, GCS polymer and corresponding dosage forms may contribute to increase the oral bioavailability of Pgp-substrate drugs, while GCS-TBA cannot be used for the same purpose.

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