Towards oral insulin-controlled release nanomedicine: A review

Frequent insulin injections remain the primary method for regulating blood glucose levels in individuals with diabetes mellitus; however, patient compliance is often poor. Due to its non-invasive nature, oral insulin delivery, exploring nanomedicine strategies, is considered a highly desirable alternative as an affordable and accessible medicine. However, the physical intestinal barriers and the harsh gastrointestinal environment provide major obstacles to reaching the best possible pharmacological bioavailability of insulin. Insulin's stability, bioavailability, and targeted administration throughout the GI tract can be improved using colloidal nanocarriers, including polymeric nanoparticles, phospholipid vesicles, and lipid-based nanoparticles. These nanocarriers mimic the physiological insulin secretion and improve the pharmacokinetics of insulin by shielding it from enzymatic degradation, facilitating controlled release, and enhancing absorption across the intestinal mucosa. Key parameters such as particle size, surface charge, zeta potential, and polymer-mucin interactions are examined concerning their effects on epithelial transport and enzymatic protection. Strategies such as PEGylation, chitosan functionalization, and bile salt incorporation are discussed with an emphasis on their interfacial engineering potential. Additionally, novel strategies such as glucose-responsive formulations, cell-penetrating peptides, and enzyme inhibitors, and innovative devices like microneedle capsules and SOMA systems have been explored to enhance oral insulin efficacy. This might not, however, be helpful for translation on its own. Another deciding aspect will be the combination of that with distinct pathways. Future perspectives and innovative approaches to enhance the therapeutic potential of nano-driven systems for oral insulin administration are also discussed in this review as an affordable and accessible medicine strategy.