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

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.

Current approaches in lipid-based nanocarriers for oral drug delivery.

Lipid-based nanocarriers have gained much interest as carriers of drugs with poor oral bioavailability because of their remarkable advantages like low toxicity, affordable scale-up manufacture, strong biocompatibility or high drug loading efficiency. The potential of these nanocarriers lies in their ability to improve the gastrointestinal stability, solubility and permeability of their cargo drugs. However, achieving efficient oral drug delivery through lipid-based nanocarriers is a challenging task, since they encounter multiple physicochemical barriers along the gastrointestinal tract, e.g. the gastric acidic content, the intestinal mucus layer or the enzymatic degradation, that they must surmount to reach their target. These limitations may be turned into opportunities through a rational design of lipid-based nanocarriers. For that purpose, this review focuses on the main challenges of the oral route indicating the strategies undertaken for lipid-based nanocarriers in order to overcome them. Understanding their shortcomings and identifying their strengths will determine the future clinical success of lipid-based nanocarriers.