North Carolina State University

Jicheng Yu

Zhen Gu

Guojun Chen

Disclosed are compositions and methods for microneedle patches comprising copolymer designed for glucose triggered insulin delivery. In one aspect, disclosed herein are microneedle patches comprising insulin loaded copolymers; wherein the insulin dissociates from the microneedle in an hyperglycemic environment; wherein the copolymer comprises poly(N-vinylpyrrolidone-co-2-N(dimethylamino)ethyl acrylate-co-3-(acrylamido)phenylboronic acid and methods of their use.

Microneedle-array patches with glucose-responsive matrix for closed-loop insulin delivery

A composition comprising an insulin-polymer conjugate and an insulin aptamer-glucagon conjugate is described. Depending upon the amount of insulin in the environment surrounding the composition, the insulin aptamer of the insulin aptamer-glucagon conjugate can bind to insulin in the insulin-polymer conjugate to form a non-covalent conjugate. When the amount of insulin in the surrounding environment rises, the insulin aptamer-glucagon conjugate can be released. Thus, the composition can be used to deliver glucagon in an insulin responsive manner. The composition can be loaded into microneedles, for example, to prepare microneedle arrays for skin patches. Methods of delivering glucagon to a subject are also described.

Insulin-responsive glucagon delivery patch

A composition comprising an amphiphilic polymeric material that is both hydrogen peroxide- and hypoxia-sensitive is described. The composition can further include a glucose-oxidizing enzyme and insulin, a bioactive derivative thereof, and/or another therapeutic agent (e.g., another diabetes treatment agent). The polymeric material can form vesicles that comprise single or multiple layers of the polymeric material that enclose the glucose-oxidizing enzyme and the insulin, bioactive derivative and/or other therapeutic agent. The vesicles can be loaded into microneedles to, for example, prepare microneedle arrays for skin patches. Methods of delivering insulin to a subject using the compositions, vesicles, microneedles, and/or microneedle array skin patches are also described.

Patch loaded with dual-sensitive vesicles for enhanced glucose-responsive insulin delivery

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 hypoxic environments 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 levels in subjects in need of such treatment.

Glucose-responsive insulin delivery microneedle system

Disclosed herein are glucose-sensitive drug delivery systems including polymeric shell encapsulating an active agent. Upon exposure to a sufficient concentration of glucose, the shell is ruptured, releasing the active agent for absorption.

Growing community of inventors

Raleigh, NC, United States of America

Jicheng Yu