Implantable micro-chip for controlled delivery of diclofenac sodium


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Abstract

We prepared an implantable micro-chip enabled for controlled delivery of diclofenac sodium (DS). The micro-chip was made of poly(methyl methacrylate), where a pair of micro-channels and micro-wells was embedded to serve as a drug diffusion barrier and a reservoir, respectively. For this purpose, the micro-channel and micro-well were filled with a water-soluble polymer, polyethylene glycol and a fine powder of DS, respectively. To modulate the drug release profile, we varied both the cross-sectional area and length of the micro-channels. Thus, the average rate and onset time of drug release could be varied from 0.32%/day to 3.68%/day and from day 0.5 to day 8, respectively, as the cross-sectional area to length ratio (i.e., A/L) of the micro-channels increased from 0.0026 mm to 0.0280 mm. To achieve both almost immediate onset and zero-order release of DS, we also prepared a micro-chip embedded with multiple pairs of the micro-wells and the micro-channels of different dimensions. In this work, a single micro-chip equipped with the micro-channels with A/Ls of 0.0280 mm, 0.0217 mm and 0.0108 mm exhibited almost zero-order drug release for 31 days (R2 > 0.996) after the release onset on day 0.5. When the resulting micro-chip was implanted in living rats, the drug concentration in the blood could be maintained at 148 ng/ml–225 ng/ml for the first 23 days while showing good biocompatibility.Graphical abstractAn implantable microchip, integrated with multiple pairs of micro-wells and micro-channels of different dimensions, can release diclofenac sodium in a zero-order pattern.

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