Exploiting the pathophysiology of the gut towards innovative oral peptide delivery strategies

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The development of new oral drug delivery systems that will enable the absorption of therapeutic peptides to the systemic circulation is one of the greatest current challenges for the pharmaceutical industry and is the ‘holy grail’ of peptide delivery. Improved novel drug delivery systems are of utmost importance in order to fulfill the potential of this route of administration in the treatment of chronic diseases (e.g. type 2 diabetes mellitus), where daily injections are often required. There are various advantages of using nanocarriers for this purpose: they offer protection against chemical and enzymatic degradation, controlled release, targeting, tolerability and/or improved uptake and translocation resulting in enhanced bioavailability and greater therapeutic efficacy. I was the first to demonstrate that lipid-based nanocarriers trigger endogenous glucagon-like peptide (GLP)-1 and GLP-2 secretion in vivo after orally administered to mice. This effect can be exploited to develop a novel and unconventional drug delivery nanosystem as a promising strategy for the treatment of gastrointestinal disorders (e.g. type 2 diabetes mellitus, Crohn’s disease, ulcerative colitis). There are significant gaps in current knowledge that need to be addressed to make this possible. I propose a series of studies to answer the following key questions: -First, can we develop a dual-action drug delivery nanosystem that synergizes its own biological effect and that of the encapsulated bioactive molecule? -Second, can we ameliorate type 2 diabetes mellitus (T2DM) and inflammatory bowel diseases (IBD) using an oral peptide-loaded dual-action lipid-based nanosystem? –Third, is this innovative strategy a viable alternative to current treatments in T2DM and IBD? By exploiting the gut pathophysiology, I propose an innovative therapeutic approach using cutting-edge advanced technologies to deal with an unmet therapeutical need in the treatment of gastrointestinal disorders.