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 Poloxamer 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.

Introduction:The conventional subcutaneous administration of insulin has been associated with several limitations leading to poor patient compliance. The poor oral bioavailability of insulin due to degradation by gastrointestinal enzymes and secretions can be countered by the use of protective carriers such as solid lipid nanoparticles that are capable of being taken up by the Peyer's patches. The aim of the investigation was to design and investigate alginate coated solid lipid nanoparticles (SLN) of insulin for oral administration. Materials and Methods: The SLN were prepared from glyceryl behenate and glyceryl monostearate and coated with mucoadhesive polymer, sodium alginate. The SLN were evaluated for size, shape, zeta potential, drug content, in vitro release and ex vivo drug permeation through goat intestinal mucosa and Caco-2 cell monolayer model. Results and Discussion: Transmission electron microscopy revealed spherical particles of uniform size distribution. In vitro drug release using the reverse dialysis method revealed that the alginate coating maintained the potency of insulin in simulated GI fluids and also provided sustained release. Absorption enhancement was demonstrated in ex vivo permeation studies in the goat intestinal mucosal model as well as in the Caco-2 cell monolayer model. The oral administration of alginate-coated insulin SLN in streptozotocin induced diabetic rats resulted in a significant hypoglycemic effect as compared to that of uncoated insulin-loaded SLN. The percentage glycemia at the end of 10 h was statistically significant (p<0.05) to oral insulin and the hypoglycemic levels reached were comparable to that of the conventional subcutaneous insulin. Conclusion: Alginate coated SLN has the potential of improving the absorption of insulin through intestinal mucosa and possibly its bioavailability.