title: Visualization of delayed release of compounds from pH-sensitive capsules in vitro and in vivo in a hamster model.
abstract: Delayed controlled release is an innovative strategy to locally administer therapeutic compounds (e.g. chemotherapeutics, antibodies etc.). This would improve efficiency and reduce side effects compared with systemic administration. To enable the evaluation of the efficacy of controlled release strategies both in vitro and in vivo, we investigated the release of contrast agents ((19)F-FDG and BaSO4) to the intestinal tract from capsules coated with pH-sensitive polymers (EUDRAGIT L-100) by using two complementary techniques, i.e. (19)F magnetic resonance imaging (MRI) and computed tomography (CT). Using in vitro (19)F-MRI, we were able to non-destructively and dynamically establish a time window of 2 h during which the capsules are resistant to low pH. With (19)F-MRI, we could establish the exact time point when the capsules became water permeable, before physical degradation of the capsule. This was complemented by CT imaging, which provided longitudinal information on physical degradation of the capsule at low pH that was only seen after 230 min. After oral administration to hamsters, (19)F-MRI visualized the early event whereby the capsule becomes water permeable after 2 h. Additionally, using CT, the integrity and location (stomach and small intestines) of the capsule after administration could be monitored. In conclusion, we propose combined (19)F-MRI and CT to non-invasively visualize the different temporal and spatial events regarding the release of compounds, both in an in vitro setting and in the gastrointestinal tract of small animal models. This multimodal imaging approach will enable the in vitro and in vivo evaluation of further technical improvements to controlled release strategies.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Dominiek
authors.initials: D
authors.lastname: Staelens
authors.affiliation: Biomedical MRI Unit/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Sayuan
authors.initials: S
authors.lastname: Liang
authors.affiliation: Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Appeltans
authors.affiliation: Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.|PharmAbs, KU Leuven, Leuven, Belgium.
authors.forename: Marlies
authors.initials: M
authors.lastname: Van de Wouwer
authors.affiliation: Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.affiliation: Biomedical MRI Unit/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich
authors.affiliation: Biomedical MRI Unit/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.
authors.forename: Greetje
authors.initials: G
authors.lastname: Vande Velde
mesh_terms: D000818:Animals; D002214:Capsules / Q000008:administration & dosage / Q000737:chemistry; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry; D006224:Cricetinae; D003692:Delayed-Action Preparations; D006863:Hydrogen-Ion Concentration; D007421:Intestine, Small / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000737:chemistry; D013270:Stomach / Q000000981:diagnostic imaging*; D014057:Tomography, X-Ray Computed
chemical_list: D002214:Capsules; D003287:Contrast Media; D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer
keywords: 19F-MRI; CT; controlled release; in vitro; multimodal imaging; pH-sensitive capsules