Macromolecule release from monodisperse PLG microspheres: control of release rates and investigation of release mechanism.
Novel macromolecular therapeutics such as peptides, proteins, and DNA are advancing rapidly toward the clinic. Because of typically low oral bioavailability, macromolecule delivery requires invasive methods such as frequently repeated injections. Parenteral depots including biodegradable polymer microspheres offer the possibility of reduced dosing frequency but are limited by the inability to adequately control delivery rates. To control release and investigate release mechanisms, we have encapsulated model macromolecules in monodisperse poly(D,L-lactide-co-glycolide) (PLG) microspheres using a double-emulsion method in combination with the precision particle fabrication technique. We encapsulated fluorescein-dextran (F-Dex) and sulforhodamine B-labeled bovine serum albumin (R-BSA) into PLG microspheres of three different sizes: 31, 44, and 80 microm and 34, 47, and 85 microm diameter for F-Dex and R-BSA, respectively. The in vitro release profiles of both compounds showed negligible initial burst. During degradation and release, the microspheres hollowed and swelled at critical time points dependant upon microsphere size. The rate of these events increased with microsphere size resulting in the largest microspheres exhibiting the fastest overall release rate. Monodisperse microspheres may represent a new delivery system for therapeutic proteins and DNA and provide enhanced control of delivery rates using simple injectable depot formulations.
Berkland
Cory
C
Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana, Illinois 61801, USA. berkland@ku.edu
Pollauf
Emily
E
Raman
Chandrashekar
C
Silverman
Roshelle
R
Kim
Kyekyoon 'Kevin'
K'
Pack
Daniel W
DW
D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D003911:Dextrans / Q000737:chemistry; D004058:Diffusion; D004337:Drug Carriers; D004339:Drug Compounding; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D012235:Rhodamines / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
D003692:Delayed-Action Preparations; D003911:Dextrans; D004337:Drug Carriers; D005452:Fluoresceins; D005456:Fluorescent Dyes; D011108:Polymers; D012235:Rhodamines; C052526:fluorescein-dextran; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; C022027:lissamine rhodamine B; D012710:Serum Albumin, Bovine; D019344:Lactic Acid