title: Noninvasive monitoring of local drug release using X-ray computed tomography: optimization and in vitro/in vivo validation.
abstract: In vivo release profiles of drug-loaded biodegradable implants were noninvasively monitored and characterized using X-ray computed tomography (CT). The imaging method was adapted and optimized to quantitatively examine the release of an active agent from a model cylindrical PLGA device (the millirod) into rabbit livers over 48 h. Iohexol, a CT contrast agent, served as a model drug; optimization of CT acquisition parameters yielded a sensitivity of 0.21 mg/mL (or 95 microg iodine/mL) for this agent. In vitro validation of the method was carried out by tracking release of iohexol in gelatin gel phantoms. In vivo release in rabbit livers was characterized through quantitative analysis of CT images and compared with UV-Vis analysis of the explanted devices at three implantation times. After correction for respiratory motion, CT analysis correlates well with the extracted iohexol data at all time points. The percent error between the actual and experimental image data was below 10%. This study demonstrates the potential of using computed tomography to noninvasively quantify the rate of agent release from controlled delivery devices in vivo.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
authors.forename: Agata
authors.initials: A
authors.lastname: Szymanski-Exner
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Stowe
authors.forename: Kyle
authors.initials: K
authors.lastname: Salem
authors.forename: Roee
authors.initials: R
authors.lastname: Lazebnik
authors.forename: John R
authors.initials: JR
authors.lastname: Haaga
authors.forename: David L
authors.initials: DL
authors.lastname: Wilson
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics; D004343:Drug Implants; D005782:Gels; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D007472:Iohexol / Q000008:administration & dosage / Q000493:pharmacokinetics; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism; D008953:Models, Anatomic; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D015203:Reproducibility of Results; D015656:Respiratory Mechanics / Q000502:physiology; D014057:Tomography, X-Ray Computed
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; D004343:Drug Implants; D005782:Gels; D004364:Pharmaceutical Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007472:Iohexol