Understanding the role of the structure of single-stimuli hybrid systems on their behaviour as platforms for colonic delivery.

ABSTRACT

The success of colon-targeted oral hybrid systems relies in the proper control over the release of the entrapped nanostructures at the colon. This work describes the design of hybrid systems for their colonic enzyme-triggered release. The hybrid systems were constituted by nanoemulsions, with adequate characteristics for the treatment of ulcerative colitis, included in a pectin hydrogel-like matrix. For that purpose, pectins with similar degrees of methylation (< 50%) and increasing degree of amidation, i.e. 0, 13 and 20%, were selected. Hybrid systems were formulated by a novel aggregation induced gelation method, using Ca2+, Ba2+ or Zn2+ as aggregating agents, as well as by a polyelectrolyte condensation approach, obtaining structures in the micrometric range (< 10 µm). Despite the resistance of pectins to the upper gastrointestinal tract stimuli, the analysis of the behaviour of the different prototypes showed that the non-covalent crosslinks that allow the formation of the hybrid structure may play a relevant role on the performance of the formulation.Our results indicated that the partial disassembling of the hybrid system's microstructure due to the intestinal conditions may facilitate the stimuli-triggered release of the nanoemulsions at the colon. More interestingly, the particle tracking experiments showed that the condensation process that occurs during the formation of the system may affect to the enzymatic degradation of pectin. In this sense, the effect of the high degree of amidation of pectin may be more prevalent as structural feature rather than as a promoter of the enzyme-triggered release.