title: Mucoadhesive properties and interaction with P-glycoprotein (P-gp) of thiolated-chitosans and -glycol chitosans and corresponding parent polymers: a comparative study.
abstract: The aim of the present work was to compare the mucoadhesive and efflux pump P-glycoprotein (P-gp) interacting properties of chitosan (CS)- and glycolchitosan (GCS)-based thiomers and corresponding unmodified parent polymers. For this purpose, the glycol chitosan-N-acetyl-cysteine (GCS-NAC) and glycol chitosan-glutathione (GCS-GSH) thiomers were prepared under simple and mild conditions. Their mucoadhesive characteristics were studied by turbidimetric and zeta potential measurements. The P-gp interacting properties were evaluated measuring the effects of thiolated- and unmodified-polymers on the bidirectional transport (BA/AB) of rhodamine-123 across Caco-2 cells as well as in the calcein-AM and ATPase activity assays. Although all the thiomers and unmodified polymers showed optimal-excellent mucoadhesive properties, the best mucoadhesive performances have been obtained by CS and CS-based thiomers. Moreover, it was found that the pretreatment of Caco-2 cell monolayer with GCS-NAC or GCS restores Rho-123 cell entrance by inhibiting P-gp activity. Hence, GCS-NAC and GCS may constitute new biomaterials useful for improving the bioavailability of P-gp substrates.
authors: Dipartimento di Farmacia-Scienze del Farmaco and ‡Dipartimento di Chimica, Università degli Studi di Bari "Aldo Moro" , Via Orabona, 4, 70125 Bari, Italy.
authors: Adriana
authors: A
authors: Trapani
authors: Claudio
authors: C
authors: Palazzo
authors: Marialessandra
authors: M
authors: Contino
authors: Maria Grazia
authors: MG
authors: Perrone
authors: Nicola
authors: N
authors: Cioffi
authors: Nicoletta
authors: N
authors: Ditaranto
authors: Nicola Antonio
authors: NA
authors: Colabufo
authors: Massimo
authors: M
authors: Conese
authors: Giuseppe
authors: G
authors: Trapani
authors: Giovanni
authors: G
authors: Puglisi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry*; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D006018:Glycols / Q000737:chemistry; D006801:Humans; D011108:Polymers / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006018:Glycols; D011108:Polymers; D013438:Sulfhydryl Compounds; C118638:glycol-chitosan; D048271:Chitosan