title: In vitro release of vascular endothelial growth factor from gadolinium-doped biodegradable microspheres.
abstract: A drug delivery vehicle was constructed that could be visualized noninvasively with MRI. The biodegradable polymer poly(DL-lactic-co-glycolic acid) (PLGA) was used to fabricate microspheres containing vascular endothelial growth factor (VEGF) and the MRI contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The microspheres were characterized in terms of size, drug and contrast agent encapsulation, and degradation rate. The PLGA microspheres had a mean diameter of 48 +/- 18 microm. The gadolinium loading was 17 +/- 3 microg/mg polymer and the VEGF loading was 163 +/- 22 ng/mg polymer. Electron microscopy revealed that the Gd was dispersed throughout the microspheres and it was confirmed that the Gd loading was sufficient to visualize the microspheres under MRI. VEGF and Gd-DTPA were released from the microspheres in vitro over a period of approximately 6 weeks in three phases: a burst, followed by a slow steady-state, then a rapid steady-state. Biodegradable Gd-doped microspheres can be effectively used to deliver drugs in a sustained manner, while being monitored noninvasively with MRI.
authors.affiliation: Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland, USA. faranesh@nih.gov
authors.forename: Anthony Z
authors.initials: AZ
authors.lastname: Faranesh
authors.forename: Monet T
authors.initials: MT
authors.lastname: Nastley
authors.forename: Cristina
authors.initials: C
authors.lastname: Perez de la Cruz
authors.forename: Michael F
authors.initials: MF
authors.lastname: Haller
authors.forename: Patrice
authors.initials: P
authors.lastname: Laquerriere
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
authors.forename: Elliot R
authors.initials: ER
authors.lastname: McVeigh
mesh_terms: D001673:Biodegradation, Environmental; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003287:Contrast Media; D004337:Drug Carriers; D019786:Gadolinium DTPA; D006801:Humans; D066298:In Vitro Techniques; D015918:Infusion Pumps, Implantable; D019344:Lactic Acid; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D003287:Contrast Media; D004337:Drug Carriers; D011108:Polymers; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019786:Gadolinium DTPA