title: MR imaging of biodegradable polymeric microparticles: a potential method of monitoring local drug delivery.
abstract: Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) was encapsulated into biodegradable, bioadhesive polymeric microparticles to enable noninvasive monitoring of their local intravesical delivery with MRI. The microparticles were characterized by contrast agent encapsulation and release kinetics, T(1) relaxation rates, and contrast enhancement in vivo. The level of Gd-DTPA loading into microparticles was 14.3 +/- 0.6 mug/mg polymer. The measured T(1) relaxation rates of the microparticles showed a direct dependence on Gd-DPTA content. Both 1.5T and 4.7T MR scanners were used to image murine bladders instilled intravesically with Gd-DTPA-loaded particles in vivo. MR images showed ring-shaped regions of enhancement inscribing the bladder wall, which were attributed to the microparticles that were preferentially adherent to the mucosa lining the urothelium. The images of controls exhibited no such enhancement. The normalized signal intensities measured from post-instillation images were significantly greater (P < 0.05) than those in the pre-instillation images. Contrast enhancement was observed for at least 5 days after the initial instillation, although the enhancement decreased due to microparticle degradation or mucosa renewal. The localized distribution of biodegradable, bioadhesive microparticles encapsulating Gd-DTPA was successfully visualized with MRI in vivo, allowing particle-mediated delivery to be temporally and spatially monitored noninvasively.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
authors.forename: Hunter H
authors.initials: HH
authors.lastname: Chen
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Visage
authors.forename: Bensheng
authors.initials: B
authors.lastname: Qiu
authors.forename: Xiangying
authors.initials: X
authors.lastname: Du
authors.forename: Ronald
authors.initials: R
authors.lastname: Ouwerkerk
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D001673:Biodegradation, Environmental; D003287:Contrast Media / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D019786:Gadolinium DTPA / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008863:Microspheres; D011108:Polymers; D001743:Urinary Bladder / Q000378:metabolism*
chemical_list: D003287:Contrast Media; D011108:Polymers; D019786:Gadolinium DTPA