title: Development and characterization of mucoadhesive chitosan films for ophthalmic delivery of cyclosporine A.
abstract: Ocular chitosan films were prepared in order to prolong ocular delivery of cyclosporine A. The mucoadhesive films were prepared using the solvent casting evaporation method. A 2(4) full factorial design was used to evaluate the effect of 4 preparation parameters on the film thickness, swelling index and mechanical properties. Moreover, uniformity of content and in vitro drug release were investigated. Possible interactions between the film excipients were studied by FTIR analysis. In vitro experiments were performed in order to evaluate the cytotoxicity and anti-inflammatory activity of the chitosan films. Film thickness, water uptake, mechanical properties and in vitro release of cyclosporine A were dependent on film composition, especially on the amount of plasticizer. Lower drug release was measured from chitosan films containing a higher amount of plasticizer as glycerol decreased the swelling of chitosan films. FTIR spectra suggest a reorganization of hydrogen bonds between chitosan chains in the presence of glycerol and cyclodextrins. None of the film formulations showed significant cytotoxicity as compared to the negative control using human epithelial cells (HaCaT). Cyclosporine A dispersed in the various film formulations remained anti-inflammatorily active as significant suppression of interleukin-2 secretion in concanavalin A stimulated Jurkat T cells was measured.
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, Antwerp (Wilrijk) 2610, Belgium. Electronic address: kris.hermans@uantwerpen.be.
authors.forename: Kris
authors.initials: K
authors.lastname: Hermans
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, Antwerp (Wilrijk) 2610, Belgium.
authors.forename: Dave
authors.initials: D
authors.lastname: Van den Plas
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, Antwerp (Wilrijk) 2610, Belgium.
authors.forename: Sabina
authors.initials: S
authors.lastname: Kerimova
authors.affiliation: Institute for Material Research (IMO), Department of Chemistry, Hasselt University, Diepenbeek, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Carleer
authors.affiliation: Institute for Material Research (IMO), Department of Chemistry, Hasselt University, Diepenbeek, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Adriaensens
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, Antwerp (Wilrijk) 2610, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Weyenberg
authors.affiliation: Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, Antwerp (Wilrijk) 2610, Belgium.
authors.forename: Annick
authors.initials: A
authors.lastname: Ludwig
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000268:Adhesiveness; D060433:Administration, Ophthalmic; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D016572:Cyclosporine / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005990:Glycerol / Q000737:chemistry; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D009092:Mucous Membrane / Q000737:chemistry; D010968:Plasticizers / Q000737:chemistry; D014867:Water / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D005079:Excipients; C508594:IL2 protein, human; D007376:Interleukin-2; D010968:Plasticizers; D047392:beta-Cyclodextrins; D014867:Water; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D016572:Cyclosporine; D048271:Chitosan; D005990:Glycerol
keywords: Chitosan; Cyclosporine A; Films; Ocular