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Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
Published on: May 2, 2019
Charge-switchable polymeric complex for glucose-responsive insulin delivery in mice and pigs
Jinqiang Wang1,2,3, Jicheng Yu3, Yuqi Zhang3
1Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.
Researchers developed a novel glucose-responsive insulin delivery system using a charge-switchable polymer complex. This system enables precise insulin release in response to high blood glucose levels, demonstrated in animal models.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Endocrinology
Background:
- Developing effective glucose-responsive insulin delivery systems remains a significant challenge, particularly for large animal models.
- Existing systems often lack robust responsiveness and precise control over insulin release.
Purpose of the Study:
- To create a micro-sized complex for glucose-responsive insulin delivery.
- To achieve high insulin loading efficiency and capacity.
- To demonstrate controlled insulin release in response to hyperglycemia.
Main Methods:
- Forming a micro-sized complex between a charge-switchable polymer and insulin via electrostatic interaction.
- Utilizing phenylboronic acid (PBA) as a glucose-sensing moiety within the polymer.
- Administering the complex via subcutaneous injection and transdermal microneedle array patch in mouse and swine models.
Main Results:
- Achieved high insulin loading efficiency (95%) and capacity (49%).
- Demonstrated glucose-triggered insulin release; PBA binds glucose, converting polymer charge and releasing insulin.
- Showcased inhibited release under normoglycemia and promoted release under hyperglycemia.
- Validated rapid, in vivo hyperglycemia-triggered insulin release in chemically induced type 1 diabetic mouse and swine models.
Conclusions:
- The developed charge-switchable polymer complex offers a promising strategy for advanced glucose-responsive insulin delivery.
- The system exhibits robust, on-demand insulin release capabilities validated in relevant animal models.
- This approach holds potential for improved diabetes management through precise glycemic control.
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