Oral bioavailability of insulin contained in polysaccharide nanoparticles.
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.
Sarmento
Bruno
B
Department of Pharmaceutical Technology, Faculty of Pharmacy of the University of Porto, 4050-047, Porto, Portugal. bruno.sarmento@ff.up.pt
Ribeiro
António
A
Veiga
Francisco
F
Ferreira
Domingos
D
Neufeld
Ronald
R
D000284:Administration, Oral; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D016264:Dextran Sulfate / Q000737:chemistry; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D011134:Polysaccharides / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar
D001672:Biocompatible Materials; D001786:Blood Glucose; D007328:Insulin; D011134:Polysaccharides; D048271:Chitosan; D016264:Dextran Sulfate