Nanocrystals, compositions, and methods that aid particle transport in mucus

A method of treating, diagnosing, or managing an ocular condition in a subject, the method comprising:

• administering a mucus-penetrating pharmaceutical composition topically to an eye of a subject, wherein the pharmaceutical composition consists of:
• A) a plurality of coated particles comprising a pharmaceutical agent, or a salt thereof, each coated particle consisting of:
• 1) a core particle comprising the pharmaceutical agent, wherein the pharmaceutical agent constitutes at least 80 wt % of the core particle, and
• 2) a mucus penetration-enhancing coating surrounding the core particle, wherein the mucus penetration-enhancing coating consists of at least one of:
• a) 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, and wherein the hydrophilic block is present at the surface of the coated particle and renders the coated particle hydrophilic,
• b) a synthetic polymer having pendant hydroxyl groups on the backbone of the polymer, the polymer having a molecular weight of at least about 1 kDa and less than or equal to about 1000 kDa, wherein the polymer is at least about 30% hydrolyzed and less than about 95% hydrolyzed, or
• c) a polysorbate,
• wherein the mucus penetration-enhancing coating is present on the outer surface of the core particle at a density of at least 0.01 molecules/nm2,
• wherein the mucus penetration-enhancing coating is present in the pharmaceutical composition in an amount of between about 0.001% and about 5% by weight;
• and
• (B) one or more ophthalmically acceptable carriers, additives, and/or diluents;
• and
• delivering the mucus-penetrating pharmaceutical composition to a tissue in the eye of the subj ect.