NANOCRYSTALS, COMPOSITIONS, AND METHODS THAT AID PARTICLE TRANSPORT IN MUCUS

摘要

Nanocrystals, compositions, and methods that aid particle transport in mucus are provided. In some embodiments, the compositions and methods involve making mucus-penetrating particles (MPP) without any polymeric carriers, or with minimal use of polymeric carriers. The compositions and methods may include, in some embodiments, modifying the surface coatings of particles formed of pharmaceutical agents that have a low water solubility. Such methods and compositions can be used to achieve efficient transport of particles of pharmaceutical agents though mucus barriers in the body for a wide spectrum of applications, including drug delivery, imaging, and diagnostic applications. In certain embodiments, a pharmaceutical composition including such particles is well-suited for administration routes involving the particles passing through a mucosal barrier.

主权项

1. A composition comprising a plurality of coated particles, wherein the coated particles comprise:
a particle core comprising one or more solid pharmaceutical agents or salts thereof, and a coating comprising a surface-altering agent surrounding the particle core;
wherein the one or more solid pharmaceutical agents or salts thereof constitutes at least about 95% of the particle core by weight;wherein the surface-altering agent comprises a triblock copolymer comprising a hydrophilic block-hydrophobic block-hydrophilic block configuration;wherein the hydrophobic block has a molecular weight of at least about 2 kDa, and the hydrophilic blocks constitute at least about 15 wt % of the triblock copolymer;wherein the hydrophobic block associates with the surface of the core particle;wherein the hydrophilic block is present at the surface of the coated particle and renders the coated particle hydrophilic;wherein the surface-altering agent is present on the surface of the core particle at a density of at least about 0.001 molecules per nanometer squared; and,wherein the coated particles have a relative velocity of greater than 0.5 in mucus.