Abstract
A key challenge for the effective treatment of gastrointestinal diseases including inflammatory bowel disease is to develop an orally administered drug delivery system capable of prolonged retention in the gastrointestinal tract. Herein we report a bioadhesive liquid coacervate based on hydrogen bonding-driven nanoparticle assembly. Free from electrostatic interactions, our fluid nanoparticle-assembled coacervate demonstrates significant pH- and salt-independent structural stability and forms a physically adhesive coating on a large surface area of intestinal tract with an extended residence time of more than 2 days to mediate the sustained release of preloaded water-soluble small molecule drugs in vivo. The orally administered drug-laden nanoparticle-assembled coacervate significantly mitigates the symptoms of inflammatory bowel disease, restores the diversity of gut microbiota, reduces systemic drug exposure, and improves the therapeutic efficacy in a rat acute colitis model compared with the oral administration of the same amount of drug in solution form. We suggest that the nanoparticle-assembled coacervate provides a promising drug delivery platform for management and treatment of numerous gastrointestinal diseases where controlled drug release with extended residence time is desired.
Highlights
A key challenge for the effective treatment of gastrointestinal diseases including inflammatory bowel disease is to develop an orally administered drug delivery system capable of prolonged retention in the gastrointestinal tract
Using the water-soluble dexamethasone sodium phosphate (Dex-P) as a model small molecule drug, we demonstrated that the oral administration of drugladen NPA coacervate significantly enhanced the Inflammatory bowel disease (IBD) therapeutic outcomes, improved the richness and diversity of gut microbiota, and reduced the systemic drug exposure compared with the treatment with Dex-P aqueous solution in a rat model of dextran sulfate sodium (DSS)-induced acute colitis—one of the most widely used models due to its shared clinical and histopathological characteristics with human IBD25 and its validation as a relevant model to treat human diseases[26]
Nanoparticles required for fabricating NPA coacervates contain a hydrophobic core and end-functionalized hydrophilic polyethylene glycol (PEG) chains as the shell (Fig. 1d)
Summary
A key challenge for the effective treatment of gastrointestinal diseases including inflammatory bowel disease is to develop an orally administered drug delivery system capable of prolonged retention in the gastrointestinal tract. Driven by the gastrointestinal peristalsis, the nanoparticle-assembled fluid coacervate (named NPA coacervate hereafter) can effectively spread to coat and adhere on the large intestinal surface area with a prolonged residence time of more than 2 days to mediate the sustained release of loaded drugs (Fig. 1c).
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