Glucose-responsive insulin delivery system using hyoxia-sensitive nanocomposites

Abstract

A closed-loop insulin delivery system is described. More particularly, the presently disclosed insulin delivery system can comprise glucose-responsive vesicles that release insulin in response to hypoxia triggered by enzymatic reduction of glucose. In addition or as an alternative to insulin, the delivery system can release other diabetes treatment agents, such as non-insulin-based diabetes treatment agents. The vesicles can be prepared from a hypoxia sensitive polymer, such as a hypoxia-sensitive hyaluronic acid (HS-HA). The HS-HA can comprise hydrophobic groups that can be reduced in hypoxicenvironments to form hydrophilic groups. The vesicles can be loaded into microneedles and microneedle array patches for use in the treatment of diabetes or to otherwise regulate blood glucose levelsin subjects in need of such treatment.

Description

[0001] related application

[0002] This application claims priority and benefit to US Provisional Patent Application No. 62 / 150,622, filed April 21, 2015, the disclosure of which is incorporated herein by reference in its entirety. technical field

[0003] The subject matter of the present disclosure relates to systems and compositions, such as vesicles, nanoparticles, microneedles and microneedle arrays, for the glucose sensitive delivery of diabetes therapeutics such as insulin and / or its biologically active derivatives. The disclosed subject matter further relates to methods of making the compositions and methods of delivering diabetes therapeutics to a subject in need thereof.

[0004] abbreviation

[0005] ℃ = degrees Celsius

[0006] % = percentage

[0007] μL = microliter

[0008] μm = micrometer or micron

[0009] μs = microsecond

[0010] a.u. = absorbance unit

[0011] BOC = tert-butoxycarbonyl

[0012] CD = circular dichroism

[0013] DI = deionized [00...

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