Title : Influence of mucoadhesivity on the bioavailability of nanoparticulate drug delivery systems
Abstract:
The oral administration route is by far the preferred one and more than 80% of drugs are taken orally. Since the gastrointestinal (GI) tract is the primary site of drug delivery, many researchers have focused their attention on the mucus layer that covers the GI tract. Indeed, the mucus can trap and coat foreign particulates and pathogens to protect the underlying epithelium so as to represent an important barrier to the absorption of nanoparticulate systems. Mucoadhesive polymeric nanoparticulate systems (NP) have raised interest as vehicles for drug delivery by the oral route, for their potential ability to improve the bioavailability of drugs with low mucosal permeability and/or poor chemical stability in the GI environment. To be absorbed across the intestinal epithelium into the systemic circulation, however, the NP will have to cross the layer of stagnant mucus adjacent to the intestinal membrane. Then, the NP tendency to adhere to the mucus gel can play an important role since on the one hand it opposes the physiologic transit of the delivery system down the GI tract away from the absorption site, thus favoring drug absorption, whereas, on the other hand, it hampers the water-driven transport of NP from luminal to epithelial side of the mucus layer, thus slowing down absorption. In fact, still open to debate is the issue of whether mucoadhesive particles prolong drug residence at the absorption site and enhance drug bioavailability or, instead, aggregate in mucus far away from the absorptive epithelium and lower the bioavailability. Recently we have demonstrated that the oral bioavailability of a drug is higher when this is trapped in a more mucoadhesive rather than in a less mucoadhesive NP type. This data was explained assuming that mucoadhesivity tends to keep the formulation at the absorption site, opposing its physiologic movement from stomach down to large intestine, while the concurrent water movement facilitates NP transport across the mucus layer from lumen to epithelium, where NP can be internalized by the cells. These results convinced us of the importance of the advective water flow present in the mucus, which can greatly influence the NP transport through it. Therefore, this presentation will be focused on the development of new methods to study the NP transport through the mucus, in particular on a method which couples the multiple particle tracking technique with the microfluidics.
Audience take away:
• Influence of polymeric NP mucoadhesivity on the bioavailability of the encapsulated drugs
• Various techniques to study NP transport through the mucus lining the GI epithelium
• Some considerations on the structure-activity relationship concerning NP having different surface characteristics
