Multicomponent insulin-containing microparticles are prepared by layer-by-layer assembly of dextran sulfate and chitosan on the core of protein-polyanion complex with or without protease inhibitors. Oral bioavailability of the encapsulated insulin is improved due to the cumulative effect of each component. A physico-chemical study shows that the particle design allows adjustment of the pH-dependent profile of the insulin release, as well as mucoadhesive properties and Ca(2+) binding ability of the microparticles. Supplementing the microparticles with 2-3% protease inhibitors fully prevents proteolysis of human insulin. The pharmacological effect of microencapsulated insulin in doses 50-100 IU kg(-1) is demonstrated in chronic experiments after oral administration to diabetic rats fed ad libitum.
Keywords: chitosan; insulin; layer-by-layer; microencapsulation; oral drug delivery systems; protease inhibitor.
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