In vitro release of vascular endothelial growth factor from gadolinium-doped biodegradable microspheres.
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.
Faranesh
Anthony Z
AZ
Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland, USA. faranesh@nih.gov
Nastley
Monet T
MT
Perez de la Cruz
Cristina
C
Haller
Michael F
MF
Laquerriere
Patrice
P
Leong
Kam W
KW
McVeigh
Elliot R
ER
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
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