Fabrication of multi-layered biodegradable drug delivery device based on micro-structuring of PLGA polymers |
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Authors: | Won Hyoung Ryu Murty Vyakarnam Ralph S Greco Fritz B Prinz Rainer J Fasching |
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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 |
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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. |
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Keywords: | Drug delivery Controlled release Micro-fabrication Biodegradable polymers PLGA |
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