Phase‐Changeable Nanoemulsions for Oral Delivery of a Therapeutic Peptide: Toward Targeting the Pancreas for Antidiabetic Treatments Using Lymphatic Transport

• Published in: Advanced functional materials Vol. 29; no. 13
• Main Authors: Lin, Po‐Yen, Chen, Kuan‐Hung, Miao, Yang‐Bao, Chen, Hsin‐Lung, Lin, Kun‐Ju, Chen, Chiung‐Tong, Yeh, Chun‐Nan, Chang, Yen, Sung, Hsing‐Wen
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 28.03.2019
• Subjects: Bioavailability; Body temperature; Deformation effects; Denaturation; Diabetes mellitus; Drug delivery systems; Epithelium; fatty acid; Fatty acids; Formability; Glucose; Insulin; intestinal lymphatic transport; Materials science; Melting points; nanoemulsion; Nanoemulsions; oral drug delivery; Pancreas; Peptides; phase change material; Phase transitions; Transport
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201809015

The oral absorption of a therapeutic peptide (such as exenatide; EXT) that can improve glycemic control in the treatment of type 2 diabetes is limited by multiple barriers of the intestinal epithelium. This work presents an oil‐structured nanoemulsion system that consists of a phase‐changeable fatty acid that allows EXT (EXT@PC/NEMs) to be delivered orally and absorbed efficiently in the small intestine. To construct an appropriate vehicle to encapsulate EXT, an oil‐in‐water single emulsion is generated at 37 °C, which is well above the melting point of the fatty acid but below the denaturation temperature of the peptide drug. The as‐prepared EXT@PC/NEMs are physically stable when stored at 4 °C, as they form a solid core, which prevents drug leakage. Upon their oral delivery at body temperature, the deformable liquid EXT@PC/NEMs may undergo effective cellular uptake, enhancing their permeability across the intestinal epithelium. The orally administered PC/NEMs significantly improve the bioavailability of EXT via intestinal lymphatic transport, ultimately accumulating in the pancreas, suggesting the possibility of orally delivering labile peptide drugs. The delivered EXT may act on pancreatic β‐ and α‐cells to stimulate insulin release and suppress glucagon secretion, respectively, reducing the blood glucose level, eventually having antidiabetic effects. Phase‐changeable nanoemulsions are used to encapsulate a peptide drug during emulsification at 37 °C and are physically stable when stored at 4 °C. Upon oral ingestion at body temperature, the deformable liquid nanoemulsions undergo effective cellular uptake, enhancing their permeability across the intestinal epithelium, ultimately accumulating in the pancreas via lymphatic transport to exert their beneficial antidiabetic effects.