PLG microsphere size controls drug release rate through several competing factors.
OBJECTIVE
Although the rate of drug release from poly(D,L-lactide-co-glycolide) (PLG) microspheres is often modulated by changing fabrication conditions or materials, the specific factors directly controlling the release profiles are often unclear. We have fabricated uniform rhodamine- and piroxicam-containing microspheres, 10 to 100 microm in diameter, to better understand how microsphere size controls drug release.


METHODS
Drug distribution within the microspheres was examined using confocal fluorescence microscopy. The rate of polymer degradation was determined as the change in molecular weight, measured by gel permeation chromatography, during in vitro degradation experiments. Further, changes in the surface and interior morphology of the particles during in vitro degradation were investigated by scanning electron microscopy.


RESULTS
Microsphere size greatly affected drug distribution. Small (approximately 10-microm) microspheres showed an essentially uniform drug distribution. Larger (approximately 100-microm) microspheres showed redistribution of drug to specific regions of the microspheres. Rhodamine partitioned to the surface and piroxicam partitioned to the interior of large PLG microspheres. Further, the rate of polymer degradation increased with microsphere size, possibly the result of a more acidic interior caused by increased accumulation of hydrolyzed polymer products in larger particles. Finally, larger microspheres developed a more porous interior structure during the drug release.


CONCLUSIONS
Microsphere size affects drug release not only through changes in diffusion rates but also through secondary effects including drug distribution in the particle, polymer degradation rate, and microsphere erosion rates.
Berkland
Cory
C
Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, Illinois 61801, USA.
Kim
Kyekyoon
K
Pack
Daniel W
DW
D019344:Lactic Acid / Q000737:chemistry* / Q000493:pharmacokinetics*; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics*
D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid