In vitro release of vascular endothelial growth factor from gadolinium‐doped biodegradable microspheres

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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 μm. The gadolinium loading was 17 ± 3 μg/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 ∼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. Magn Reson Med 51:1265–1271, 2004. Published 2004 Wiley‐Liss, Inc.