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

Abstract

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.

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“…The effect of surfactant type was investigated; where SLN containing Poloxamer 407 showed a significantly ( p < 0.05) smaller particle size compared to those containing Tween 80 with and without CS coating. These findings are in accordance with the results previously reported by Anchan et al [ 39 ] and may be attributed to the increased deposition of CS on SLNs’ surface triggered by the decreased solubility in presence of Tween 80 compared with Poloxamer 407 [ 39 ]. CS-coated SLNs (F3, F4) showed a significant increase in particle size compared to uncoated SLNs (F1, F2).…”

“…This faster permeation may prove beneficial in protecting the phytoconstituents from the harsh metabolizing environment of the oral route. These findings are in line with those previously reported by Anchan et al [ 39 ], who reported the ability of CS-coated insulin-loaded SLNs to enhance insulin intestinal permeation compared to uncoated SLNs and free insulin [ 39 ].…”

“…SLNs were prepared by the solvent evaporation method using GMS and either Poloxamer 407 or Tween 80 as surfactants. In order to increase the SLNs mucoadhesive properties, improve the nanocarrier permeation through the gastrointestinal mucosa, and decrease their burst release, SLNs were coated with CS [ 38 , 39 ].…”

“…Poloxamer 407 containing formulations, such as F1 and F3, had higher % EE compared to F2 and F4 containing Tween 80. This might be attributed to the greater solubilizing effects of Poloxamer 407 compared to Tween 80 [ 39 ]. Furthermore, CS-SLNs such as F3 had higher EE % compared to uncoated SLNs (F1), namely 79% and 74 %, respectively.…”

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“…At the end of an 8 h trial, the oral administration of chitosan-coated insulin SLN to STZinduced diabetic rats resulted in a substantial hypoglycemic impact (p < 0.05) as compared to groups receiving uncoated insulin-loaded SLN or the oral insulin solution, which was equivalent to subcutaneous insulin. Chitosan-coated SLN can be an efficient oral insulin formulation [92].…”