Abstract

AbstractThe oral route is considered to be the most convenient and comfortable means of drug administration for patients. Nevertheless, oral administration of hydrophilic macromolecules such as peptide/protein drugs is encountered with many difficulties. To overcome these difficulties, a pH‐sensitive nanoparticle (NP) carrier system, self‐assembled by chitosan (CS) and poly‐γ‐glutamic acid (γ‐PGA), is developed for paracellular transports of insulin. Oral administration of insulin‐loaded NPs shows a significant hypoglycemic action in diabetic rats and the corresponding relative bioavailability of insulin is approximately 15%. These findings suggest that the developed NP system is a promising carrier for improved transmucosal delivery of insulin in the small intestine. Besides insulin, this NP carrier system is expected to serve as a platform for oral delivery of hydrophilic macromolecules such as pharmaceutically active peptides/proteins, glycosaminoglycans, and oligonucleotides. Studies on the detailed mechanism of tight‐junction opening by CS or its derivatives are in progress, which is of paramount importance and needs to be established to aid further development in the use of NPs for oral delivery of hydrophilic macromolecules.

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