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Calcitonin And Insulin In Isobutylcyanoacrylate Nanocapsules: Protection Against Proteases And Effect On Intestinal Absorption In Rats

Philip J Lowe, Cathy S Temple

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Abstract One of the major limiting steps for the absorption of peptide drugs from the intestine is proteolytic degradation. To slow this degradation, human calcitonin was trapped in polyacrylamide nanoparticles, and human calcitonin and insulin were encapsulated with polyisobutylcyanoacrylate. Human calcitonin trapped in polyacrylamide nanoparticles showed no delayed release characteristics and thus would not provide protection from proteases. Proteolytic degradation of human calcitonin and insulin in polyisobutylcyanoacrylate nanocapsules was slower than the free peptides in solution. The plasma pharmacokinetic profiles were consistent with increased survival time of the peptides in the intestine, with higher plasma concentrations of the peptides in the later time samples compared with the controls. However, the nanocapsules gave no significant overall enhancement of peptide absorption. This led to the conclusion that the nanocapsules released the peptides into the intestinal lumen, with small amounts then being absorbed but the rest largely degraded.