NANOPARTICLE FORMULATIONS WITH ENHANCED MUCOSAL PENETRATION

摘要

Hypotonic formulations were evaluated for delivering water-soluble drugs and for drug delivery with muco-inert (that is, non-adhesive) mucus-penetrating nanoparticles (MPP). Hypotonic formulations markedly increased the rate at which drugs and MPP reached the epithelial surface, including deep into the vaginal folds. Minimally hypotonic formulations, preferably ranging from 20-220 mOsm/kg, provided rapid and uniform delivery of MPP to the entire vaginal surface, with minimal risk of epithelial toxicity. Data also show that there is a higher osmolality in the colon, such that vehicles with an osmolality above that of blood plasma (generally considered isotonic at ˜300 mOsm/kg), still lead to improvements in distribution in the colon due to rapid, osmotically-induced fluid absorption. The range for improved colon distribution with a hypotonic vehicle in the colon is ˜20 mOsm/kg-450 mOsm/kg.

主权项

1. A hypotonic formulation comprising mucus penetrating particles, the particles comprising a mucus penetration enhancing coating and a therapeutic, prophylactic, diagnostic or nutraceutical agent for administration to a mucosal tissue, the formulation being hypotonic for the epithelium to which it is delivered, such that the formulation causes water uptake by the epithelium as revealed by the rapid transport of the mucus-penetrating nanoparticles to, and more uniform coverage of, the epithelial surface. where they provide sustained mucosal delivery of the agent.