University of Innsbruck, Pharmaceutical Technology, Innrain 52c, Innsbruck, 6020 Austria.
The aim of this study was to develop a novel nanoparticulate formulation and test its potential for oral peptide drug delivery. Chitosan-6-mercaptonicotinic acid is a novel thiolated chitosan with strong mucoadhesive properties. Nanoparticles were developed by an ionic gellation method. The obtained particles were characterized in terms of mucoadhesion, stability, toxicity, and in vitro release. Human insulin (HI) was chosen as a model peptide drug, incorporated in the particles and orally administered to rats. Human insulin was quantified in the blood by means of ELISA. The size of the obtained particles was in the range of 200-300 nm and the zeta potential was determined to be +8-+23 depending on the amount of thiol groups attached on the polymer. After 3 h of incubation up to 60% of the thiolated chitosan nanoparticles remained attached to the mucosa in contrast to 20% of unmodified chitosan particles. The AUC of HI after oral administration of thiolated chitosan nanoparticles was 4-fold improved compared to unmodified chitosan nanoparticles. Due to these improvements, chitosan-6-mercaptonicotinic acid nanoparticles are promising vehicles for oral delivery of peptide drugs.