title: Implantable micro-chip for controlled delivery of diclofenac sodium.
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.
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Min
authors.initials: M
authors.lastname: Park
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Chun Gwon
authors.initials: CG
authors.lastname: Park
authors.affiliation: Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul 110-799, Republic of Korea.
authors.forename: Byung-Hwi
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea.
authors.forename: SungYoon
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: So-rae
authors.initials: SR
authors.lastname: Nam
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul 110-799, Republic of Korea.
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Park
authors.affiliation: Interdisciplinary Program in Bioengineering, College of Engineering, Seoul National University, Seoul 152-742, Republic of Korea; Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea; Institute of Medical & Biological Engineering, Medical Research Center, Seoul National University, Seoul 110-799, Republic of Korea. Electronic address: ybchoy@snu.ac.kr.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Choy
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004343:Drug Implants; D008838:Microcomputers; D019904:Polymethyl Methacrylate; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004343:Drug Implants; D004008:Diclofenac; D019904:Polymethyl Methacrylate
keywords: Controlled delivery; Diclofenac sodium; Micro-channel; Micro-chip; Zero-order release; poly(methyl methacrylate)