The oral route is the most preferred route of drug administration. It is easy to administer, pain free and cheaper compared to other routes of administration. However, this route is sometimes inefficient due to the partial/inadequate absorption of the drug, first-pass metabolism, the instability of the drug in harsh gastrointestinal conditions (such as intestinal pH or enzyme degradation). There is an unmet need for the administration of biologics via the oral route of administration, especially in the treatment of chronic diseases where a daily painful administration is often required.
The aim of our research is developing improved alternative drug delivery systems to fulfill the potential of the oral route of administration. For this purpose, we are exploiting the unique pathophysiology of the gut towards the development of novel drug delivery strategies, focusing on the treatment of two main chronic diseases: type 2 diabetes mellitusand inflammatory bowel diseases. Our recent results describe a novel nanosystem compatible with human use that synergizes its ownbiological effect with the effects of increasing thebioavailability of a GLP-1 analogue. The effects of thef ormulation were comparable to the results observed for the marketed subcutaneous formulation. This nanocarrier-based strategy represents a novel promising approach for oral peptide delivery in incretin-based diabetes treatment. A schematic representation of our strategy is depicted in Figure 1.
Figure 1: A schematic representation of the dual effect attained with our novel nanoformulation (from Xu et al., J Control Release, 2020)
Unraveling the mechanisms of nanoparticle transport across the intestinal barrier is essential for designing more efficient nanoparticles for oral administration. For this purpose, we have development in vitromodels of the intestinal epithelium and follicle-associated epithelium containing M cells to evaluate the mechanisms of transport of our drug delivery systems at the intestinal site. In concrete, we study the physicochemical parameters that dictate the fate of the drug delivery systems across the intestinal barrier. This includes evaluating targeting strategies that could potentially ameliorate the transport of our drug delivery systems across the intestinal epithelium (Figure 2).
Figure 2: Targeting strategies towardsthe intestinal barrier(from Xu et al., J Control Release, 2020)