Oral Bioavailability of Insulin Contained in Polysaccharide Nanoparticles

• Author(s): Sarmento, Bruno ; Ribeiro, António ; Veiga, Francisco ; Ferreira, Domingos ; Neufeld, Ronald
• Date: 2007
• Persistent ID: http://hdl.handle.net/10316/10566
• Origin: Estudo Geral - Universidade de Coimbra
• Document Type: Article
• Language: English

Description

The pharmacological activity of insulin-loaded dextran sulfate/chitosan nanoparticles was evaluated following oral dosage in diabetic rats. Nanoparticles were mucoadhesive and negatively charged with a mean size of 500 nm, suitable for uptake within the gastrointestinal tract. Insulin association efficiency was over 70% and was released in a pH-dependent manner under simulated gastrointestinal conditions. Orally delivered nanoparticles lowered basal serum glucose levels in diabetic rats around 35% with 50 and 100 IU/kg doses sustaining hypoglycemia over 24 h. Pharmacological availability was 5.6 and 3.4% for the 50 and 100 IU/kg doses, respectively, a significant increase over 1.6%, determined for oral insulin alone in solution. Confocal microscopic examinations of FITC-labeled insulin nanoparticles showed adhesion to rat intestinal epithelium, and internalization of insulin within the intestinal mucosa. Encapsulation of insulin into dextran sulfate/chitosan nanoparticles was a key factor in the improvement of the bioavailability of its oral delivery over insulin solution. http://dx.doi.org/10.1021/bm0703923