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  • In vitro and in vivo testing of glucose-responsive insulin-delivery microdevices in diabetic rats.

In vitro and in vivo testing of glucose-responsive insulin-delivery microdevices in diabetic rats.

Lab on a chip (2012-05-09)
Michael K L Chu, Jian Chen, Claudia R Gordijo, Simon Chiang, Alexander Ivovic, Khajag Koulajian, Adria Giacca, Xiao Yu Wu, Yu Sun
ABSTRACT

We have developed glucose-responsive implantable microdevices for closed-loop delivery of insulin and conducted in vivo testing of these devices in diabetic rats. The microdevices consist of an albumin-based bioinorganic membrane that utilizes glucose oxidase (GOx), catalase (CAT) and manganese dioxide (MnO(2)) nanoparticles to convert a change in the environmental glucose level to a pH stimulus, which regulates the volume of pH-sensitive hydrogel nanoparticles and thereby the permeability of the membrane. The membrane is integrated with microfabricated PDMS (polydimethylsiloxane) structures to form compact, stand-alone microdevices, which do not require tethering wires or tubes. During in vitro testing, the microdevices showed glucose-responsive insulin release over multiple cycles at clinically relevant glucose concentrations. In vivo, the microdevices were able to counter hyperglycemia in diabetic rats over a one-week period. The in vitro and in vivo testing results demonstrated the efficacy of closed-loop biosensing and rapid response of the 'smart' insulin delivery devices.

MATERIALS
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Manganese(IV) oxide, activated, ~85%, <10 μm
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Manganese(IV) oxide, 10 μm, reagent grade, ≥90%
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Sigma-Aldrich
Manganese(IV) oxide, ReagentPlus®, ≥99%
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