Nanoparticle-assembled bioadhesive coacervate coating with prolonged gastrointestinal retention for inflammatory bowel disease therapy

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.

Mucus interaction to improve gastrointestinal retention and pharmacokinetics of orally administered nano-drug delivery systems

“…Harloff-Helleberg et al [ 178 ] explored the mucoadhesive behavior of sucrose acetate isobutyrate (SAIB) and found an 11-fold increase in intestinal residence time when compared to a free solution. Zhao et al [ 179 ] developed a nanoparticle self-assembled bioadhesive coacervate coating for inflammatory bowel disease treatment and demonstrated a retention time of more than 2 days and improved efficacy (as shown by a four to sixfold improvement in colonic histopathology score) when compared to an untreated control and oral administration of a solution of the drug.…”

Mucosa-interfacing electronics

“…Typical mucoadhesive mechanisms involve non-covalent interactions, such as hydrogen bonding, hydrophobic interactions, electrostatic interactions, mechanical interlocking and interdiffusion of polymer chains; the efficacy of these interactions also depends on surface properties, such as roughness, and the ability to move water away from the hydrated mucus interface 131 . Mucoadhesion can be further strengthened through the formation of covalent bonds, for instance, by reactions between alkene groups and the thiol groups present in the cysteine residue of mucin 131 , or by incorporating microsized and nanosized particles into adhesives to increase the surface area-to-volume ratio of the mucoadhesive materials 132 . Existing mucoadhesive materials are primarily used for prolonged drug delivery at various sites of action, including the nasal cavity 133 , vaginal lumen 134 and digestive tract (for example, the oral cavity 135 , 136 , intestinal lumen 137 , 138 and colon 139 , 140 ).…”

Mucoadhesive probiotic backpacks with ROS nanoscavengers enhance the bacteriotherapy for inflammatory bowel diseases

“…However, because of their rapid clearance, nonspecific drug biodistribution after systemic administration, and relatively inefficient ROS-scavenging ability, antioxidants demonstrate inconsistent efficacy for treating inflammatory diseases. Furthermore, undesirable drug distribution profiles of antioxidants in normal tissues can cause a variety of adverse effects (17)(18)(19).…”