title: Ex vivo permeation of tamoxifen and its 4-OH metabolite through rat intestine from lecithin/chitosan nanoparticles.
abstract: Tamoxifen citrate is an anticancer drug slightly soluble in water. Administered orally, it shows great intra- and inter-patient variations in bioavailability. We developed a nanoformulation based on phospholipid and chitosan able to efficiently load tamoxifen and showing an enzyme triggered release. In this work the permeation of tamoxifen released from lecithin/chitosan nanoparticles across excised rat intestinal wall mounted in an Ussing chamber was investigated. Compared to tamoxifen citrate suspension, the amount of the drug permeated using the nanoformulation was increased from 1.5 to 90 times, in absence or in presence of pancreatin or lipase, respectively. It was also evidenced the formation of an active metabolite of tamoxifen, 4-hydroxy tamoxifen, however, the amount of metabolite permeated remained roughly constant in all experiments. The effect of enzymes on intestinal permeation of tamoxifen was shown only when tamoxifen-loaded nanoparticles were in intimate contact with the mucosal surface. The encapsulation of tamoxifen in lecithin/chitosan nanoparticles improved the non-metabolized drug passing through the rat intestinal tissue via paracellular transport.
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/a, 43124 Parma, Italy; Interdepartmental Centre for Innovation in Health Products, Biopharmanet-TEC, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Barbieri
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/a, 43124 Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Buttini
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/a, 43124 Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rossi
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/a, 43124 Parma, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bettini
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/a, 43124 Parma, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Colombo
authors.affiliation: CNRS UMR 8612, Université de Paris Sud XI, Faculté de Pharmacie, 5 rue J.B. Clément, 92296 Châtenay-Malabry, France.
authors.forename: G
authors.initials: G
authors.lastname: Ponchel
authors.affiliation: Department of Pharmacy, University of Parma, Parco Area delle Scienze 27/a, 43124 Parma, Italy; Graduate School of Health Pharmacy, University of Technology Sydney, Broadway, NSW 2007, Australia. Electronic address: fabio.sonvico@unipr.it.
authors.forename: F
authors.initials: F
authors.lastname: Sonvico
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara 17/19, 44121 Ferrara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Colombo
mesh_terms: D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D054709:Lecithins / Q000737:chemistry*; D008049:Lipase / Q000737:chemistry; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010194:Pancreatin / Q000737:chemistry; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D004337:Drug Carriers; D054709:Lecithins; D013629:Tamoxifen; D010194:Pancreatin; D048271:Chitosan; D008049:Lipase
keywords: Chitosan; Intestinal permeation; Nanoparticles; Oral chemotherapy; Tamoxifen citrate