Engineering Glucose-Responsive Insulin Granules with High-Payload for Long-Acting Glycemic Control.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Endocrinology

Background:

• Developing high-payload drug delivery systems is critical for enhancing protein therapy precision, safety, and patient compliance.
• Controlling protein release from these carriers in response to physiological changes remains a significant challenge.
• Insulin (Ins) delivery requires dynamic response to blood glucose fluctuations for effective diabetes management.

Purpose of the Study:

• To engineer a physiology-responsive, high-payload insulin granule for sustained glucose management.
• To overcome the limitations of conventional insulin therapy, such as short duration of action and frequent administration.
• To develop an intelligent delivery system for protein therapeutics with improved safety and efficacy.

Main Methods:

• Fabrication of [(Ins&GOx)@Zn]@[TA&Fe] granules with high insulin loading capacity.
• In vitro and in vivo evaluation of glucose-responsive insulin release and glucose-lowering effects.
• Assessment of long-term administration safety, including physiological toxicity and immune response.

Main Results:

• Achieved an insulin loading capacity exceeding 80%, substantially higher than previous reports (≈40%).
• Extended the glucose-regulating effect of insulin from 3 hours to 6 days with a single injection.
• Demonstrated no significant physiological toxicity or immune response during 28-day administration.

Conclusions:

• The developed physiology-responsive, high-payload insulin granules offer a promising strategy for long-term glucose management.
• This approach advances the development of intelligent delivery systems for protein therapeutics, improving precision, safety, and patient compliance.
• The engineered granules represent a significant step towards more effective and patient-friendly diabetes treatments.