title: Fabrication of multi-layered biodegradable drug delivery device based on micro-structuring of PLGA polymers.
abstract: A programmable and biodegradable drug delivery device is desirable when a drug needs to be administered locally. While most local drug delivery devices made of biodegradable polymers relied on the degradation of the polymers, the degradation-based release control is often limited by the property of the polymers. Thus, we propose micro-geometry as an alternative measure of controlling drug release. The proposed devices consist of three functional layers: diffusion control layer via micro-orifices, diffusion layer, and drug reservoir layers. A micro-fabrication technology was used to shape an array of micro-orifices and micro-cavities in 85/15PLGA layers. A thin layer of fast degrading 50/50PLGA was placed as the diffusion layer between the 85/15PLGA layers to prevent any burst-type release. To modulate the release of the devices, the dimension and location of the micro-orifices were varied and the responding in vitro release response of tetracycline was monitored over 2 weeks. The release response to the different micro-geometry was prominent and further analyzed by FEM simulation. Comparison of the experiments to the simulated results identified that the variation of micro-geometry influenced also the volume-dependent degradation rate and induced the osmotic pressure.
authors.affiliation: Rapid Prototyping Laboratory, Mechanical Engineering Department, Stanford University, Rm. 226, Bldg. 530, 440 Escondido Mall, Stanford, CA 94305, USA. whryu@stanford.edu
authors.forename: Won Hyoung
authors.initials: WH
authors.lastname: Ryu
authors.forename: Murty
authors.initials: M
authors.lastname: Vyakarnam
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Greco
authors.forename: Fritz B
authors.initials: FB
authors.lastname: Prinz
authors.forename: Rainer J
authors.initials: RJ
authors.lastname: Fasching
mesh_terms: D020341:Absorbable Implants; D001672:Biocompatible Materials / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D044085:Microfluidics / Q000379:methods*; D008863:Microspheres; D008904:Miniaturization; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D013752:Tetracycline / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013752:Tetracycline