title: Fabrication of PLG microspheres with precisely controlled and monodisperse size distributions.
abstract: The size distribution of biodegradable polymer microspheres critically impacts the allowable routes of administration, biodistribution, and release rate of encapsulated compounds. We have developed a method for producing microspheres of precisely controlled and/or monodisperse size distributions. Our apparatus comprises spraying a polymer-containing solution through a nozzle with (i) acoustic excitation to produce uniform droplets, and (ii) an annular, non-solvent carrier stream allowing further control of the droplet size. We used this apparatus to fabricate poly(D,L-lactide-co-glycolide) (PLG) spheres. The acoustic excitation method, by itself, produced uniform microspheres as small as 30 microm in diameter in which > or =95% of the spheres were within 1.0-1.5 microm of the average. The carrier stream method alone allowed production of spheres as small as approximately 1-2 microm in diameter from a 100-microm diameter nozzle, but generated broader size distributions. By combining the two devices, we fabricated very uniform spheres with average diameters from approximately 5 to >500 microm. Furthermore, by discretely or continuously varying the experimental parameters, we fabricated microsphere populations with predefined size distributions. Finally, we demonstrate encapsulation and in vitro release of a model drug compound, rhodamine B. In summary, our apparatus provides unprecedented control of microsphere size and may allow development of advanced controlled-release delivery systems.
authors.affiliation: Department of Chemical Engineering, University of Illinois, Urbana, IL 61801, USA.
authors.forename: C
authors.initials: C
authors.lastname: Berkland
authors.forename: K
authors.initials: K
authors.lastname: Kim
authors.forename: D W
authors.initials: DW
authors.lastname: Pack
mesh_terms: D000465:Algorithms; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D019344:Lactic Acid / Q000737:chemistry*; D008854:Microscopy, Electron; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry; D014465:Ultrasonics
chemical_list: D004337:Drug Carriers; D011108:Polymers; D012235:Rhodamines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C029773:rhodamine B