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

Amit Fischer, Sivan Lilienthal, Margarita Vázquez-González, Michael Fadeev, Yang Sung Sohn, Rachel Nechushtai, Itamar Willner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


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 Zn2+-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.

Original languageAmerican English
Pages (from-to)4223-4234
Number of pages12
JournalJournal of the American Chemical Society
Issue number9
StatePublished - 4 Mar 2020

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© 2020 American Chemical Society.


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