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 method for treating an eye disease or disorder in a patient in need thereof, comprising:
administering to an eye of the patient a pharmaceutical composition comprising:
a plurality of particles, wherein each of the particles comprises a biocompatible core and a surface-altering moiety disposed on the core that reduces mucoadhesion of the particle, wherein the surface-altering moiety comprises a hydrophilic polymer or a copolymer comprising PEG or a derivative of PEG, wherein the surface-altering moiety is uncharged or substantially neutrally charged, and wherein the surface-altering moiety is present on the core at a density of greater than 0.01 units per nanometer squared; and
a therapeutically effective amount of a bioactive agent.
78 . A method for treating an eye disease or disorder in a patient in need thereof, comprising:
administering to an eye of the patient a pharmaceutical composition comprising:
a plurality of particles, wherein each of the particles comprises a biocompatible core and a surface-altering moiety disposed on the core that reduces mucoadhesion of the particle, wherein the surface-altering moiety comprises a hydrophilic polymer or a copolymer comprising PEG or a derivative of PEG, wherein the surface-altering moiety is uncharged or substantially neutrally charged, and wherein the surface-altering moiety is present on the core at a density of greater than 0.01 units per nanometer squared; and
a therapeutically effective amount of a corticosteroid.
79 . A pharmaceutical composition for treating an eye disease or disorder in a patient in need thereof by administration to an eye of the patient, comprising:
a plurality of particles, wherein each of the particles comprises a biocompatible core and a surface-altering moiety disposed on the core that reduces mucoadhesion of the particle, wherein the surface-altering moiety comprises a hydrophilic polymer or a copolymer comprising PEG or a derivative of PEG, wherein the surface-altering moiety is uncharged or substantially neutrally charged, and wherein the surface-altering moiety is present on the core at a density of greater than 0.01 units per nanometer squared; and
a therapeutically effective amount of a bioactive agent.
80 . A pharmaceutical composition for treating an eye disease or disorder in a patient in need thereof by administration to an eye of the patient, comprising:
a plurality of particles, wherein each of the particles comprises a biocompatible core and a surface-altering moiety disposed on the core that reduces mucoadhesion of the particle, wherein the surface-altering moiety comprises a hydrophilic polymer or a copolymer comprising PEG or a derivative of PEG, wherein the surface-altering moiety is uncharged or substantially neutrally charged, and wherein the surface-altering moiety is present on the core at a density of greater than 0.01 units per nanometer squared; and
a therapeutically effective amount of a corticosteroid.
81 . The method of claim 77 , wherein the surface-altering moiety is a hydrophilic polymer.
82 . The method of claim 81 , wherein the hydrophilic polymer comprises PEG.
83 . The method of claim 82 , wherein the PEG has a molecular weight of approximately 1 kDa, approximately 2 kDa, approximately 3 kDa, approximately 4 kDa, approximately 6 kDa, or approximately 8 kDa.
84 . The method of claim 77 , wherein the surface-altering moiety is a copolymer of PEG.
85 . The method of claim 84 , wherein the surface-altering moiety is a copolymer comprising PEG having a molecular weight of approximately 1 kDa, approximately 2 kDa, approximately 3 kDa, approximately 4 kDa, approximately 6 kDa, or approximately 8 kDa.
86 . The method of claim 77 , wherein the surface-altering moiety comprises a block copolymer of oxyethylene and oxypropylene.
87 . The method of claim 77 , wherein the surface-altering moiety is a poloxamer.
88 . The method of claim 77 , wherein the surface-altering moiety is present on the outer surface of the particle at a density of greater than 0.05 molecules per nanometer squared.
89 . The method of claim 77 , wherein the surface-altering moiety is present on the outer surface of the particle at a density of greater than 0.1 molecules per nanometer squared.
90 . The method of claim 77 , wherein the surface-altering moiety is covalently attached to the core.
91 . The method of claim 77 , wherein the surface-altering moiety is non-covalently adsorbed to the core.
92 . The method of claim 77 , wherein the mass of the surface-altering moiety makes up at least 1/3400 of the mass of the particle.
93 . The method of claim 77 , wherein the particle is larger than 1 nm and less than 1000 nm in diameter.
94 . The method of claim 93 , wherein the particle is between 100-500 nm in diameter.
95 . The method of claim 77 , wherein the particle has a zeta potential between −10 mV and +10 mV.
96 . The method of claim 77 , wherein the particle further comprises a targeting moiety.
97 . The method of claim 77 , wherein the step of administering comprises administering the pharmaceutical composition topically to the eye of the patient.
98 . The method of claim 97 , wherein the step of administering comprises administering the pharmaceutical composition in the form of eye drops.
99 . The method of claim 77 , wherein the step of administering comprises administering the pharmaceutical composition to the eye of the patient by injection.
100 . The method of claim 98 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
101 . The method of claim 100 , wherein the pharmaceutical composition comprises a stabilizer.
102 . The method of claim 101 , wherein the stabilizer is a salt.
103 . The method of claim 102 , wherein the pharmaceutically acceptable carrier is glycerin.
104 . The method of claim 77 , wherein the bioactive agent is present in the core of the particle.
105 . The method of claim 104 , wherein the bioactive agent is a corticosteroid.
106 . The pharmaceutical composition of claim 79 , wherein the surface-altering moiety is a hydrophilic polymer.
107 . The pharmaceutical composition of claim 106 , wherein the hydrophilic polymer comprises PEG.
108 . The pharmaceutical composition of claim 107 , wherein the PEG has a molecular weight of approximately 1 kDa, approximately 2 kDa, approximately 3 kDa, approximately 4 kDa, approximately 6 kDa, or approximately 8 kDa.
109 . The pharmaceutical composition of claim 79 , wherein the surface-altering moiety is a copolymer of PEG.
110 . The pharmaceutical composition of claim 109 , wherein the surface-altering moiety is a copolymer comprising PEG having a molecular weight of approximately 1 kDa, approximately 2 kDa, approximately 3 kDa, approximately 4 kDa, approximately 6 kDa, or approximately 8 kDa.
111 . The pharmaceutical composition of claim 79 , wherein the surface-altering moiety comprises a block copolymer of oxyethylene and oxypropylene.
112 . The pharmaceutical composition of claim 79 , wherein the surface-altering moiety is a poloxamer.
113 . The pharmaceutical composition of claim 79 , wherein the surface-altering moiety is present on the outer surface of the particle at a density of greater than 0.05 molecules per nanometer squared.
114 . The pharmaceutical composition of claim 79 , wherein the surface-altering moiety is present on the outer surface of the particle at a density of greater than 0.1 molecules per nanometer squared.
115 . The pharmaceutical composition of claim 79 , wherein the surface-altering moiety is covalently attached to the core.
116 . The pharmaceutical composition of claim 79 , wherein the surface-altering moiety is non-covalently adsorbed to the core.
117 . The pharmaceutical composition of claim 79 , wherein the mass of the surface-altering moiety makes up at least 1/3400 of the mass of the particle.
118 . The pharmaceutical composition of claim 79 , wherein the particle is larger than 1 nm and less than 1000 nm in diameter.
119 . The pharmaceutical composition of claim 118 , wherein the particle is between 100-500 nm in diameter.
120 . The pharmaceutical composition of claim 79 , wherein the particle has a zeta potential between −10 mV and +10 mV.
121 . The pharmaceutical composition of claim 79 , wherein the particle further comprises a targeting moiety.
122 . The pharmaceutical composition of claim 79 , wherein the pharmaceutical composition is adapted for topically delivery to the eye of the patient.
123 . The pharmaceutical composition of claim 122 , wherein the pharmaceutical composition is in the form of eye drops.
124 . The pharmaceutical composition of claim 79 , wherein the pharmaceutical composition is adapted for delivery to the eye of the patient by injection.
125 . The pharmaceutical composition of claim 123 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
126 . The pharmaceutical composition of claim 125 , wherein the pharmaceutical composition comprises a stabilizer.
127 . The pharmaceutical composition of claim 126 , wherein the stabilizer is a salt.
128 . The pharmaceutical composition of claim 127 , wherein the pharmaceutically acceptable carrier is glycerin.
129 . The pharmaceutical composition of claim 79 , wherein the bioactive agent is present in the core of the particle.
130 . The pharmaceutical composition of claim 129 , wherein the bioactive agent is a corticosteroid.