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Intestinal iontophoresis from mucoadhesive patches: a strategy for oral delivery

Banerjee, Amrita, Chen, Renwei, Arafin, Shamsul, Mitragotri, Samir
Journal of controlled release 2019 v.297 pp. 71-78
bioadhesives, bioavailability, blood glucose, drugs, electric current, hypoglycemia, insulin, intestines, permeability, tight junctions
Biologics have limited permeability across the intestine and are prone to degradation in the acidic-proteolytic milieu of the gastrointestinal tract, leading to poor oral bioavailability. Iontophoresis is a promising technology that can substantially improve transport of drugs across biological barriers and has been particularly explored for skin. In this study, we investigated whether iontophoresis across the intestine can be utilized to improve oral insulin transport. Application of electric current to intestinal cells resulted in opening of the tight junctions in vitro and a consequent about 3-fold improvement in paracellular transport of insulin. When evaluated in vivo using insulin-loaded mucoadhesive patches, iontophoresis produced profound hypoglycemia (63% blood glucose drop in 3 h) without damaging the intestinal tissue and the efficacy depended on insulin dose and current density. This study presents a proof of principle for intestinal iontophoresis as a novel method for oral protein delivery.