title: Poly(acrylic acid)-cysteine for oral vitamin B12 delivery.
abstract: The aim of this study was to investigate the potential of poly(acrylic acid)-cysteine (PAA-cys) solution and microparticles to enhance the transport of vitamin B12 (VB 12) across Caco-2 cell monolayer and rat intestinal mucosa. Thiolated PAA was synthesized by covalent attachment of L-cysteine. Microparticles were prepared by spray-drying and characterized regarding their size, morphology, thiol group content, VB 12 payload and release, swelling behavior, mucoadhesion, permeation-enhancing effect, and cytotoxicity. Particles with a mean diameter of 2.452±2.26 μm, a payload of 1.11±0.72%, and 190.2±8.85 μmol of free thiol groups per gram were prepared. Swelling behavior studies revealed that the stability of thiolated particles was improved compared with unmodified ones. Of the total VB 12 loaded, 95±0.12% was released within 3 h from thiolated particles. PAA-cys particles exhibited 2.24-fold higher mucoadhesive properties compared with unmodified particles. Permeation experiments with Caco-2 cells proved that permeability of VB 12 with PAA-cys solution and particles was 3.8- and 3.6-fold higher than control, respectively, and with rat intestinal mucosa it was 4.8- and 4.4-fold higher than control, respectively. Negligible cytotoxicity was assessed. PAA-cys is a promising excipient for oral delivery of VB 12 as a solution and as microparticles.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria.
authors.forename: Federica
authors.initials: F
authors.lastname: Sarti
authors.forename: Javed
authors.initials: J
authors.lastname: Iqbal
authors.forename: Christiane
authors.initials: C
authors.lastname: Müller
authors.forename: Gul
authors.initials: G
authors.lastname: Shahnaz
authors.forename: Deni
authors.initials: D
authors.lastname: Rahmat
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage* / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D003545:Cysteine / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000180:Acrylic Resins; C006903:carbopol 940; D003545:Cysteine; D014805:Vitamin B 12