Oral Glucose-Responsive Nanocarrier System for Management of Diabetes

Rahul Maurya, Suman Ramteke, Pranay Guru, Narendra Kumar Jain


Background: The regulation of postprandial blood glucose concentration in a diabetic person is a toilsome task by the conventional approaches. The continuous monitoring and subcutaneous injection of insulin are always imperative for diabetes management. To overcome the hurdle associated with the conventional system, a glucose-responsive nanoparticle (NP)-based approach was developed for oral insulin administration. The objective of the work is the formulation and characterization of a nanocarrier-based bio-responsive, self-regulated oral insulin drug delivery system.

Methods: The mannose ligand-conjugated NPs were prepared by the inotropic gelation method in which insulin and glucose oxidase enclosed alginate nanocarrier cross-linked by tripolyphosphate. The prepared NPs were filled into the enteric-coated capsule and their release profile was determined at different pH and glucose concentrations. NPs were characterized by size distribution, % drug entrapment, enzyme activity, and in vivo and in vitro drug release studies.

Results: The average size, surface potential, % drug entrapment of optimized NPs were 245.52 3.37 nm, 22.12 2.13, and 76.151.3%, respectively. The release of insulin from optimized NPs (GOx-ALG-MCNPs) (98.560.06%) occurs only at higher sugar concentrations (? 400 mg/dL) and prevents the release at low sugar concentrations (< 100 mg/dL). The enteric capsule shell protected the formulation to the gastric environment upon oral administration and directed them into the intestine. Mucoadhesion characteristics of NPs prolonged intestinal retention to make them available for cellular uptake. Glucose sensitivity and glucose-dependent effect on different pH environments study revealed that NPs released the drug only at higher concentrations of sugar solution while inhibiting the release at normal and lower sugar concentrations. Besides, compared to other prepared formulations, the GOx-ALG-MCNPs displayed controlled insulin release in response to glucose concentration.

Conclusions: An important finding of GOx-ALG-MCNPs is auto-regulating, glucose-responsive behavior imparting a significantly controlled lowering of blood glucose in an animal model. The findings reveal that the developed glucose-responsive NPs may prove to be a potential strategy for oral insulin delivery.

J Endocrinol Metab. 2022;12(4-5):146-160
doi: https://doi.org/10.14740/jem747


Bio-responsive; Diabetes; Insulin; Nanoparticle; Oral delivery

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