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 biologicals via the oral route of administration, especially in the treatment of chronic diseases where a daily painful administration is 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 mellitus and inflammatory bowel diseases. Our recent results have shown the ability of lipid-based nanocapsules to induce endogenous GLP-1 and GLP-2 secretion (Figure 1).
Figure 1: Size effect on lipid nanocapsule-mediated GLP-1 secretion from enteroendocrine L cells (from Xu et al, Mol. Pharm., 2018)
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 vitro models 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 (Figure 2).