title: Glucose-driven chemo-mechanical autonomous drug-release system with multi-enzymatic amplification toward feedback control of blood glucose in diabetes.
abstract: A second-generation novel chemo-mechanical autonomous drug release system, incorporating various improvements over our first-generation system, was fabricated and evaluated. Enhanced oxygen uptake by the enzyme membrane of the organic engine was facilitated by optimizing the quantity of enzyme immobilizer, PVA-SbQ, and by hydrophobizing the membrane surface. Various quantities of PVA-SbQ were evaluated in the organic engine by measuring the decompression rate, with 1.5 mg/cm(2) yielding optimum results. When fluororesin was used as a hydrophobizing coating, the time to reach the peak decompression rate was shortened 2.3-fold. The optimized elements of the system were evaluated as a unit, first in an open loop and then in a closed loop setting, using a mixture of glucose solution (25 mmol/L), ATP and MgCI2 with glucose hexokinase enzyme (HK) as a glucose reducer. In conclusion, feedback-control of physiologically relevant glucose concentration was demonstrated by the second-generation drug release system without any requirement for external energy.
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Munkhbayar
authors.initials: M
authors.lastname: Munkhjargal
authors.affiliation: Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Kohdai
authors.initials: K
authors.lastname: Hatayama
authors.affiliation: Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsuura
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Toma
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Arakawa
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan; Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. Electronic address: m.bdi@tmd.ac.jp.
authors.forename: Kohji
authors.initials: K
authors.lastname: Mitsubayashi
mesh_terms: D015374:Biosensing Techniques; D001786:Blood Glucose; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004800:Enzymes, Immobilized / Q000737:chemistry; D005947:Glucose / Q000737:chemistry / Q000378:metabolism*; D006593:Hexokinase / Q000737:chemistry; D006801:Humans; D019397:Pancreas, Artificial
chemical_list: D001786:Blood Glucose; D004800:Enzymes, Immobilized; D006593:Hexokinase; D005947:Glucose
keywords: Artificial pancreas; Chemo-mechanical; Enzyme membrane; Hexokinase