NSTI Nanotech 2009

Chitosan as mucoadhesive agent to enhance absorption of therapeutic proteins encapsulated into solid lipid nanoparticles

J. Teixeira, A. Júlio, C. Castro, J. Fonseca, S. Martins, D. Ferreira, B. Sarmento
University of Porto, PT

Keywords: chitosan, insulin, oral delivery, SLN, mucoadhesion


The aim of this work was to develop Witepsol 85E solid lipid nanoparticles (SLN) containing insulin as biopharmaceutical, and to evaluate their potential for oral insulin administration. The new carrier was coated with chitosan in an innovative way regarding optimum mucoadhesive properties and the ability to transiently open tight junctions. SLN and chitosan-coated SLN were prepared by a modified solvent emulsification-evaporation method. Particle size, zeta potential and entrapment efficiency were determined by PCS, LDA and HPLC, respectively. Caco-2 cells seeded on Snapwell filters were used to in vitro transport studies. Insulin pharmacological activity was determined in diabetic animals and insulin internalization through intestinal tissue tracked by confocal microscopy. Insulin-loaded SLN possessed homogenous size distribution around 300 nm and negative zeta potential. Size slightly increase after chitosan coating and charge to positive values. The association efficiency of insulin was around 45%. Insulin in vitro transport increased after encapsulation into SLN and mainly into chitosan-coated SLN. Insulin-loaded SLN decreased glycemia comparing to control, and hypoglycemic effect was more pronounced when SLN were coated with chitosan. New chitosan-coated SLN were found suitable carrier systems for the administration of insulin through the oral route, contributing for the development of an optimized oral insulin formulation.
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