Biodistribution and pharmacokinetics of thiolated chitosan nanoparticles for oral delivery of insulin in vivo

• Published in: International journal of biological macromolecules Vol. 150; pp. 281 - 288
• Main Authors: Sudhakar, Sekar, Chandran, S. Viji, Selvamurugan, Nagarajan, Nazeer, Rasool Abdul
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2020
• Subjects: Administration, Oral; Animals; Bioavailability; Biological Availability; Chemical Phenomena; Chitosan; Chitosan - chemistry; Drug Carriers - chemistry; Drug Delivery Systems; Drug Liberation; Insulin; Insulin - administration & dosage; Insulin - pharmacokinetics; Mucoadhesion; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Oral delivery; Particle Size; Rats; Spectroscopy, Fourier Transform Infrared; Sulfhydryl Compounds - chemistry; Tissue Distribution; Chitosan; Bioavailability; Mucoadhesion; Insulin; Oral delivery
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.02.079

To improve the quality of life of diabetic patients, oral delivery of insulin would be better than subcutaneous injection, and the encapsulation of insulin for its oral delivery is a promising alternative one. In this study, we prepared an oral insulin delivery system using thiolated chitosan nanoparticles (TCNPs) loaded with insulin (Ins) and tested under in vitro and in vivo systems. TCNPs prepared from CS and pentaerythritol tetrakis (3-mercaptopropionate) (PETMP) at 4:1 ratio showed 220 ± 4 nm, 2.3 ± 1 mV, and 119 ± 4 μmol g−1 in their size, charge and sulfhydryl content, respectively. There was a sustained release of insulin from the TCNPs at pH 5.3. TCNPs treatment did not alter cell viability in vitro and oral administration of TCNPs reached over the tip of the microvilli near the intestinal mucosa in vivo. There were increased and decreased the levels of insulin and glucose in the blood, respectively when Ins-TCNPs were orally administered in the diabetes induced rats. Thus, our results suggested that the insulin stays significantly for a prolonged period to make bio-distribution and bioavailability due to its interaction with the mucus of the intestine, thus offering a better oral insulin delivery system for diabetic patients. •Chemical modification and characterization of thiolated chitosan nanoparticles-Insulin (TCNPs-Ins) using PETMP•Proposed the structure-activity relationship and sustained release of TCNPs-Ins at in vitro•TCNPs facilitate a prolonged residence time of orally delivered insulin in the ileum region of Wister rat by FITC conjugation.