Oral Insulin Delivery in a Physiologic Context: Review

Arbit, Ehud; Kidron, Miriam

doi:10.1177/1932296817691303

Cited by 65 publications

(42 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Orally delivered insulin could significantly enhance patient compliance. In addition, it would closely mimic the physiological path of pancreatic insulin (2,3). Oral/pancreatic insulin is transported to the liver via the portal vein where 80% is retained and the rest reaches systemic circulation, creating up to threefold higher insulin concentration in the portal vein compared with systemic circulation (3).…”

mentioning

confidence: 99%

Ionic liquids for oral insulin delivery

Banerjee

Ibsen

Brown

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

308

227

View full text Add to dashboard Cite

With the rise in diabetes mellitus cases worldwide and lack of patient adherence to glycemia management using injectable insulin, there is an urgent need for the development of efficient oral insulin formulations. However, the gastrointestinal tract presents a formidable barrier to oral delivery of biologics. Here we report the development of a highly effective oral insulin formulation using choline and geranate (CAGE) ionic liquid. CAGE significantly enhanced paracellular transport of insulin, while protecting it from enzymatic degradation and by interacting with the mucus layer resulting in its thinning. In vivo, insulin-CAGE demonstrated exceptional pharmacokinetic and pharmacodynamic outcome after jejunal administration in rats. Low insulin doses (3-10 U/kg) brought about a significant decrease in blood glucose levels, which were sustained for longer periods (up to 12 hours), unlike s.c. injected insulin. When 10 U/kg insulin-CAGE was orally delivered in enterically coated capsules using an oral gavage, a sustained decrease in blood glucose of up to 45% was observed. The formulation exhibited high biocompatibility and was stable for 2 months at room temperature and for at least 4 months under refrigeration. Taken together, the results indicate that CAGE is a promising oral delivery vehicle and should be further explored for oral delivery of insulin and other biologics that are currently marketed as injectables.

show abstract

mentioning

confidence: 99%

Ionic liquids for oral insulin delivery

Banerjee

Ibsen

Brown

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

308

227

View full text Add to dashboard Cite

show abstract

“…Based on the characteristics of AX gels, this work aims to obtain insulin‐loaded AX microspheres and evaluate their characteristics and in vitro release when insulin‐glutamic acid mixtures are used. This system could work as a colon‐targeted system and complement the subcutaneous insulin therapy in diabetic patients by impacting hepatic mechanisms involved in glucose regulation as has been previously proposed …”

Section: Introductionmentioning

confidence: 95%

“…Nevertheless, one of the main advantages suggested for oral insulin administration is the ability to follow the natural physiological insulin route, which means that once absorbed, insulin is directed first to the liver via portal circulation and later transported to peripheral tissues . In contrast to a significant number of drugs, it has been proposed that the hepatic first‐pass metabolism of insulin may be beneficial and provide a better glucose regulation while reducing peripheral hyperinsulinemia . However, protein and peptide drugs may be degraded by the acidic and proteolytic activity in the stomach and small intestine when taken orally .…”

Section: Introductionmentioning

confidence: 99%

Tailoring reversible insulin aggregates loaded in electrosprayed arabinoxylan microspheres intended for colon‐targeted delivery

Morales‐Burgos¹,

Carvajal–Millán²,

Rascón‐Chu³

et al. 2019

J of Applied Polymer Sci

View full text Add to dashboard Cite

Arabinoxylans (AX) covalent gels are little affected by pH changes and fermentable by colonic microbiota, which make them suitable for insulin oral administration and colon-targeted delivery. In this work, the tailoring of insulin aggregates size using glutamic acid and their loading in AX microspheres (2%w/v) prepared by triaxial electrospray is presented. Dynamic light scattering showed that insulin-glutamic acid aggregates are reversible under intestinal conditions. AX microspheres presented a spherical shape, a mean diameter of 233 μm, a heterogeneous microstructure as shown by scanning electron microscopy, and a homogeneous distribution of insulin aggregates as observed by confocal laser scanning microscopy. In this AX-insulin system, 20% of insulin is released under simulated gastrointestinal pH conditions, indicating that most of the insulin stays into the microspheres, available for colonic release.

show abstract

“…Still, despite drawbacks, and the complex and challenging task of producing oral insulins, the research in the field is intense and widespread . Alone in the United States, there are currently more than 30 active clinical studies, and oral insulin formulations are moving through the pharmaceutical company pipelines in the quest to be first on the market …”

Section: Introductionmentioning

confidence: 99%