title: In vitro evaluation of glycol chitosan based formulations as oral delivery systems for efflux pump inhibition.
abstract: 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.
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Via Orabona 4, 70125 Bari, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Mandracchia
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Via Orabona 4, 70125 Bari, Italy. Electronic address: adriana.trapani@uniba.it.
authors.forename: Adriana
authors.initials: A
authors.lastname: Trapani
authors.affiliation: Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tripodo
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Via Orabona 4, 70125 Bari, Italy. Electronic address: mariagrazia.perrone@uniba.it.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Perrone
authors.affiliation: Department of "Scienze e Tecnologie Biologiche, Chimiche, Farmaceutiche (STEBICEF)", University of Palermo, via Archirafi 32, Palermo 90123, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giammona
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Via Orabona 4, 70125 Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Trapani
authors.affiliation: Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Via Orabona 4, 70125 Bari, Italy.
authors.forename: Nicola Antonio
authors.initials: NA
authors.lastname: Colabufo
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D006018:Glycols / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D006018:Glycols; D048271:Chitosan
keywords: 2- iminothiolane (PubChem CID: 433941); 5,5′-Dithiobis(2-nitrobenzoic acid) (PubChem CID: 6254); Caco-2 cells; Glycol chitosan-4-thiobutylamidine thiomer; Glycol chitosan-based formulations; Oral bioavailability; P-gp inhibition properties; Rhodamine 123; Rhodamine 123 (PubChem CID 65217); Sodium tripolyphosphate (PubChem CID: 24455); dl-Dithiothreitol (PubChem CID: 446094); l-Cysteine hydrochloride (PubChem CID: 60960)