Boosting the oral absorption of insulin using Ultrafine bubbles

Abstract

Ultrafine bubbles (UFBs), which have a diameter < 1 μm, are renowned for their stability in liquid because of the effects of Brownian motion. The unique physicochemical properties and diverse biological effects of UFBs have potential industrial and biological applications. One important property of UFBs is their negative surface charge, which is thought to be able to influence the positively charged intestinal enzymatic activity and to increase peptide drug mucosal absorption. In this study, insulin was used as the peptide drug model and administered to rats both intestinally and orally at different concentrations of UFB solution to examine the effects of UFBs on the mucosal absorption of insulin. The UFB solution promoted mucosal insulin absorption. Increasing the number of UFBs in solution increased both ileal and oral insulin absorption. To identify the mechanism responsible for this increased insulin absorption, we examined insulin degradation in pepsin and trypsin solutions and found that the presence of UFBs slowed insulin degradation. The biological safety of UFBs in water was evaluated to examine their potential future health applications. UFBs did not affect common blood biochemical parameters or the health of organs and mucosal membranes. To our knowledge, this is the first study to provide evidence for the effects of UFBs in water on oral insulin absorption. In conclusion, the use of UFBs in water represents a novel method for increasing the oral absorption of peptide drugs, such as insulin. UFBs may be promising candidates as a delivery tool for clinical drug development.