Oral Insulin Delivery by Chitosan Coated Solid Lipid Nanoparticles: Ex vivo and in vivo Studies

Objectives: The objective of this investigation was to formulate chitosan coated, insulin-loaded solid lipid nanoparticles (SLN) for oral administration and investigate their potential as an effective alternative to the subcutaneous injection. Methods: The SLN were prepared from glyceryl monostearate and coated with the mucoadhesive polymer, chitosan and were investigated for physical properties, ex vivo permeation through Caco-2-cell monolayer and goat intestinal mucosa. The in vivo efficacy of the optimized formulation in controlling blood glucose levels was studied in streptozotocin induced diabetic rats. Results: Coating in the presence of Poloxamer 407 resulted in significantly smaller nanoparticles than those with Tween 80. Scanning electron microscopy and transmission electron microscopy revealed spherical particles of uniform size distribution. The insulin association efficiency and loading efficiency of SLN prepared with Raloxamer were much greater than those with Tween 80. Ex vivo permeability studies in Caco-2 cell monolayer revealed a 4 fold increase in insulin permeation from chitosan coated SLN (P< 0.005) as compared to uncoated SLN at the end of 6 h. The percentage permeation through excised sheep intestinal mucosa from coated SLN was twice that from uncoated SLN and nearly 20 times from insulin solution. The oral administration of chitosan-coated insulin SLN to streptozotocin-induced diabetic rats resulted in a significant hypoglycemic effect (P<0.05) when compared to the groups that received uncoated insulin-loaded SLN or the oral insulin solution and was comparable to that of subcutaneous insulin at the end of an 8 h study. Conclusion: Chitosan coated SLN can be considered promising as an effective oral insulin formulation.