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Triggered Release of Loads from Microcapsule-in-Microcapsule Hydrogel Microcarriers: En-Route to an "Artificial Pancreas"

Journal of the American Chemical Society, 2020-03, Vol.142 (9), p.4223 [Peer Reviewed Journal]

EISSN: 1520-5126 ;DOI: 10.1021/jacs.9b11847 ;PMID: 32031792

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  • Title:
    Triggered Release of Loads from Microcapsule-in-Microcapsule Hydrogel Microcarriers: En-Route to an "Artificial Pancreas"
  • Author: Fischer, Amit ; Lilienthal, Sivan ; Vázquez-González, Margarita ; Fadeev, Michael ; Sohn, Yang Sung ; Nechushtai, Rachel ; Willner, Itamar
  • Subjects: Cadmium Compounds - chemistry ; Calcium Carbonate - chemistry ; Capsules - chemistry ; Dextrans - chemistry ; DNA, Catalytic - chemistry ; Drug Carriers - chemistry ; Drug Liberation ; Fluorescent Dyes - chemistry ; Glucose - chemistry ; Glucose Oxidase - chemistry ; Hydrogels - chemistry ; Insulin - chemistry ; Pancreas, Artificial ; Quantum Dots - chemistry ; Rhodamines - chemistry ; Selenium Compounds - chemistry ; Sulfides - chemistry ; Zinc Compounds - chemistry
  • Is Part Of: Journal of the American Chemical Society, 2020-03, Vol.142 (9), p.4223
  • Description: A method to assemble stimuli-responsive nucleic acid-based hydrogel-stabilized microcapsule-in-microcapsule systems is introduced. An inner aqueous compartment stabilized by a stimuli-responsive hydrogel-layer (∼150 nm) provides the inner microcapsule (diameter ∼2.5 μm). The inner microcapsule is separated from an outer aqueous compartment stabilized by an outer stimuli-responsive hydrogel layer (thickness of ∼150 nm) that yields the microcapsule-in-microcapsule system. Different loads, e.g., tetramethyl rhodamine-dextran (TMR-D) and CdSe/ZnS quantum dots (QDs), are loaded in the inner and outer aqueous compartments. The hydrogel layers exist in a higher stiffness state that prevents inter-reservoir or leakage of the loads from the respective aqueous compartments. Subjecting the inner hydrogel layer to Zn -ions and/or the outer hydrogel layer to acidic pH or crown ether leads to the triggered separation of the bridging units associated with the respective hydrogel layers. This results in the hydrogel layers of lower stiffness allowing either the mixing of the loads occupying the two aqueous compartments, the guided release of the load from the outer aqueous compartment, or the release of the loads from the two aqueous compartments. In addition, a pH-responsive microcapsule-in-microcapsule system is loaded with glucose oxidase (GOx) in the inner aqueous compartment and insulin in the outer aqueous compartment. Glucose permeates across the two hydrogel layers resulting in the GOx catalyzed aerobic oxidation of glucose to gluconic acid. The acidification of the microcapsule-in-microcapsule system leads to the triggered unlocking of the outer, pH-responsive hydrogel layer and to the release of insulin. The pH-stimulated release of insulin is controlled by the concentration of glucose. While at normal glucose levels, the release of insulin is practically prohibited, the dose-controlled release of insulin in the entire diabetic range  is demonstrated. Also, switchable ON/OFF release of insulin is achieved highlighting an autonomous glucose-responsive microdevice operating as an "artificial pancreas" for the release of insulin.
  • Publisher: United States
  • Language: English
  • Identifier: EISSN: 1520-5126
    DOI: 10.1021/jacs.9b11847
    PMID: 32031792
  • Source: MEDLINE
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