Glucose-responsive smart polymeric nanocarriers for oral insulin delivery: Design, optimization, and preclinical evaluation

Title : Glucose-responsive smart polymeric nanocarriers for oral insulin delivery: Design, optimization, and preclinical evaluation

Abstract:

Background: Oral insulin delivery remains a long-standing challenge due to enzymatic degradation and poor intestinal permeability. Glucose-responsive smart polymeric nanocarriers represent an emerging strategy to enable self-regulated insulin release while improving bioavailability. This study aimed to develop and optimize a phenylboronic acid-functionalized polymeric nanoparticle system for glucose-triggered oral insulin delivery.

Methods: Insulin-loaded glucose-responsive nanoparticles (GR-NPs) were fabricated using a modified double-emulsion solvent evaporation method. A Box–Behnken experimental design was applied to optimize polymer ratio, crosslinking density, and surfactant concentration. Particle size, PDI, zeta potential, encapsulation efficiency, and in vitro glucose-triggered release were evaluated. Protection against simulated gastric and intestinal fluids was assessed. Caco-2 permeability studies and in vivo hypoglycemic efficacy were investigated in streptozotocin-induced diabetic rat models.

Results: Optimized GR-NPs exhibited a mean diameter of 168 ± 9 nm, PDI 0.19, and zeta potential of −14 mV. Encapsulation efficiency reached 81.6%. The nanoparticles demonstrated minimal insulin release (<12%) under normoglycemic conditions (5 mM glucose) but showed significantly enhanced release (68% over 6 h) under hyperglycemic conditions (20 mM glucose). In simulated gastric fluid, insulin degradation was reduced by 74% compared to free insulin. Apparent permeability (Papp) across Caco-2 monolayers increased 3.1-fold. In vivo studies showed a sustained hypoglycemic effect for up to 14 hours with a relative bioavailability of 18.4%, compared to subcutaneous insulin.

Conclusion: The developed glucose-responsive nanocarrier system demonstrates promising potential for self-regulated oral insulin delivery, improving stability, permeability, and therapeutic efficacy. This platform may represent a significant step toward non-invasive diabetes management and scalable smart oral biologics.

Keywords: Oral Insulin, Glucose-Responsive Nanoparticles, Smart Drug Delivery, Phenylboronic Acid, Polymeric Nanocarriers, Diabetes Therapy

Biography:

Sobhan Yousefi, PhD in Biotechnology and a young professor at Islamic Azad University in Iran. He is currently working as the youngest professor. He is the author of 12 books and more than 36 reputable scientific articles and a reviewer of highly reputable scientific journals. He is also a collaborator on many research projects. He is also a consultant to the pharmaceutical and pharmaceutical industries in Iran and the Persian Gulf countries.