Nanomedicine Journal

Nanomedicine Journal

Recent advances in nanocarriers and advanced formulation strategies for oral insulin delivery

Articles in Press

Document Type : Review Paper

Authors
Munirah Munirah 1
Dudi Hardianto 1
Efrida Martius 1
Juwartina Ida Royani 2
Laras Novitasari 3
Ronny Martien 3
1 Research Centre for Vaccine and Drugs Development, National Research and Innovation Agency (BRIN), South Tangerang, Banten, Indonesia
2 Research Centre for Estate Crops, National Research and Innovation Agency (BRIN), South Tangerang, Banten, Indonesia
3 Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Indonesia
10.22038/nmj.2026.94780.2405
Abstract
Diabetes mellitus currently affects an estimated 635 million individuals worldwide. Insulin therapy remains the primary treatment option for patients with type 1 diabetes and those with type 2 diabetes who are unable to achieve adequate glycemic control. However, conventional subcutaneous insulin administration poses challenges to patient compliance and quality of life. In contrast, oral insulin offers a promising alternative by mimicking the physiological pathways of insulin secretion and hepatic metabolism, potentially reducing peripheral hyperinsulinemia and the risk of hypoglycemia. Despite this potential, physiological barriers to oral insulin remain, including enzymatic degradation in the gastrointestinal tract, limited epithelial permeability, and entrapment in the mucus layer. Accordingly, this review aims to synthesize recent advances in oral insulin formulation, with a particular focus on strategies to overcome these barriers, nanotechnology-based delivery systems, and their clinical applications. A comprehensive literature analysis was conducted, emphasizing nanocarrier platforms such as polymeric nanoparticles and metal-organic frameworks. Complementary strategies, such as enteric coatings and absorption enhancers, were also examined for their roles in improving intestinal bioavailability and enabling controlled insulin release. Early-phase preclinical and clinical data suggest that these systems can improve therapeutic outcomes and patient adherence. Various formulation approaches have demonstrated the ability to protect insulin from enzymatic degradation and enhance intestinal transport. Despite promising progress, significant challenges remain in long-term safety, scalable manufacturing, and regulatory approval. Future progress will require interdisciplinary innovations in materials science, biomanufacturing, and data-driven optimization, including artificial intelligence. Overall, nanotechnology-enabled oral insulin delivery represents a next-generation therapeutic strategy with significant potential to transform diabetes management and improve patients' quality of life.
Keywords
Bioavailability
Diabetes mellitus
Drug delivery systems
Insulin
Nanoparticles
Subjects
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Available Online from 01 September 2026