Compositions and Methods for Enhancing Transport Through Mucus
The invention generally relates to compositions and methods for transporting substances across mucosal barriers. The invention also relates to methods of making and using such substances.
1 .- 76 . (canceled)
77 . A particle comprising a core, an outer surface, and one or more surface-altering moieties disposed on the outer surface that reduce mucoadhesion of the particle, wherein the one or more surface-altering moieties are present on the outer surface at a density of greater than 0.01 units per nanometer squared, wherein the surface-altering moiety is a poloxamer, wherein said core is
(i) a pharmaceutically acceptable polymer core;
(ii) a core having one or more bioactive agents; or
(iii) a pharmaceutically acceptable polymer core, wherein a bioactive agent is encapsulated in the core; and
wherein the surface-altering moiety is disposed on the outer surface by adsorption or covalent linkage.
78 . The particle of claim 77 , wherein the particle core comprises a polymer.
79 . The particle of claim 78 , wherein the polymer comprises surface-altering moieties disposed on the outer surface.
80 . The particle of claim 77 , wherein one or more bioactive agents are associated with the particle.
81 . The particle of claim 77 , wherein the particle has a particle size between 150 μm and 750 μm in diameter.
82 . The particle of claim 77 , wherein the particle has a particle size between 150 μm and 500 μm in diameter.
83 . The particle of claim 80 , wherein the bioactive agent is an imaging agent or a therapeutic agent.
84 . The particle of claim 77 , wherein the surface-altering moiety has a density of at least 0.02, of at least 0.05, of at least 0.1, of at least 0.2, of at least 0.5, of at least 1, of at least 2, of at least 5, of at least 10, or of at least 20 units per nanometer squared.
85 . The particle of claim 77 , wherein the particle has a zeta potential between −10 mV and 10 mV, between −10 mV and 5 mV, between −5 mV and 5 mV, or between −2 mV and 2 mV.
86 . The particle of claim 77 , whereby the particle moves in human cervicovaginal mucus at a diffusivity of more than 4×10 −2 μm 2 /s at a time scale of 1 s.
87 . The particle of claim 77 , wherein the mass of the surface-altering moiety makes up about 1/3400, about 1/200, about 1/1000, about 1/500, about 1/200, about 1/100, about 1/50, about 1/20, about ⅕, about ½, or about 9/10 of the mass of the particle.
88 . The particle of claim 77 , wherein said core is (ii) a core having one or more bioactive agents or (iii) a pharmaceutically acceptable polymer core, wherein a bioactive agent is encapsulated in the polymer core; and the bioactive agent is hydrophobic, comprises hydrogen bond donors or acceptors, or is charged.
89 . The particle of claim 77 , wherein the poloxamer comprises a poly(ethylene) glycol block having a molecular weight of about 300 Da, about 600 Da, about 1 kDa, about 2 kDa, about 3 kDa, or about 4 kDa.
90 . A pharmaceutical composition comprising the particle of claim 77 and one or more pharmaceutically acceptable carriers.
91 . An ophthalmic formulation comprising the particle of claim 77 .
92 . The ophthalmic formulation of claim 91 , further comprising one or more pharmaceutically acceptable carriers.
93 . A method for treating or diagnosing an ophthalmic condition in a patient, comprising administering to the eye of the patient the pharmaceutical composition of claim 90 .