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 surface-altering moiety is a poloxamer, 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;
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;
wherein the surface-altering moiety is disposed on the outer surface by adsorption or covalent linkage; and
wherein the particle has a particle size between 150 nm and 750 nm in diameter.
78 . The particle of claim 77 , wherein the core is (i) a pharmaceutically acceptable polymer core, or (iii) a pharmaceutically acceptable polymer core, wherein a bioactive agent is encapsulated in the core.
79 . The particle of claim 77 , wherein the 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 core.
80 . The particle of claim 77 , wherein the particle has a particle size between 200 nm and 750 nm in diameter.
81 . The particle of claim 77 , wherein the particle has a particle size between 150 nm and 500 nm in diameter.
82 . The particle of claim 79 , wherein the bioactive agent is an imaging agent or a therapeutic agent.
83 . The particle of claim 77 , wherein the particle has a zeta potential of 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.
84 . 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.
85 . 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.
86 . 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, or about 2 kDa.
87 . The particle of claim 77 , wherein the core is hydrophobic, comprises one or more hydrogen bond donors or acceptors, or is charged.
88 . The particle of claim 77 , wherein the core comprises a pharmaceutically acceptable polymer selected from poly(D,L-lactic-co-glycolic) acid, polyethylenimine, dioleyltrimethylammoniumpropane/dioleyl-sn-glycerolphosphoethanolamine, and polysebacic anhydride.
89 . The particle of claim 77 , wherein the mass of the surface-altering moiety makes up at least 1/3400, 1/2000, 1/1000, 1/500, 1/200, 1/100, 1/50, 1/20, ⅕, ½, or 9/10 of the mass of the particle.
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 .