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Fabrication of multi-layered biodegradable drug delivery device based on micro-structuring of PLGA polymers
Authors:Won Hyoung Ryu  Murty Vyakarnam  Ralph S Greco  Fritz B Prinz  Rainer J Fasching
Institution:(1) Rapid Prototyping Laboratory, Mechanical Engineering Department, Stanford University, Rm. 226, Bldg. 530, 440 Escondido Mall, Stanford, CA 94305, USA;(2) Center for Biomaterials and Advanced Technologies, Ethicon Inc, Johnson & Johnson, Rt. 22 West, Somerville, NJ 08876, USA;(3) Surgery Department, School of Medicine, Stanford University, Rm H3691, 300 Pasteur Dr., Stanford, CA 94305, USA
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.
Keywords:Drug delivery  Controlled release  Micro-fabrication  Biodegradable polymers  PLGA
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