Oral peptides: Mesoporous silicon loaded ionic liquids and trypsin inhibitors to promote oral absorption of semaglutide

Abstract

Ionic liquids (ILs), as solvents, permeation enhancers, and stabilizers of drugs, has achieved some success in the field of oral delivery of insoluble drugs. However, ILs still face different challenges in the oral delivery of peptides. Among them, the biggest problem would be the large amount of water in the human digestive tract which will rapidly dilute and dissociate IL, resulting in the rapid release of peptides in the gastrointestinal tract. Then the peptides will be degraded and inactivated by digestive enzymes, and it will be difficult to achieve adequate bioavailability. The purpose of this study was to use mesoporous silica microparticles (MSM) loaded with IL, semaglutide, and Soy-derived pancreatic enzyme inhibitors at the same time, to overcome the disadvantages of oral ILs oral and to enhance the oral absorption of semaglutide. Enteric coating was used to concentrate the release of drugs and ILs in the intestine. The IL used in this study was sorbic choline synthesized from sorbate and choline bicarbonate. In vitro dissolution study showed that the enteric coating could protect semaglutide from release in low pH conditions or artificial gastric juice, with less than 10% of semaglutide released at 2h end point. At the same time, more than 90% of semaglutide was released within half an hour in pH 6.8 buffer or artificial intestinal juice. After oral administration, enteric MSM loading semaglutide, trypsin inhibitors and ILs (EMSM-Sema-TI-IL) significantly increased the bioavailability of semaglutide compared with oral Rybelsus®, although further experimental confirmation is needed. In conclusion, this MSM preparation has the potential to be an oral delivery platform for peptide drugs.