GROWTH FACTOR FORMULATION FOR CONDITION ASSOCIATED WITH OTIC EVENT
Disclosed herein are otic formulations and compositions comprising growth factors. These otic formulations and compositions allow for the delivery of the growth factor to the outer, middle, and/or inner ear for the treatment of otic diseases and disorders.
1 . A method of treating an otic disease or condition associated with a synapses-affecting event in a subject in need thereof, the method comprising administering an otic formulation comprising a therapeutically effective amount of a growth factor and an auris-acceptable vehicle within 14 days after onset of the synapses-damaging event, wherein the otic formulation is formulated to provide sustained release of the growth factor into the inner ear to promote formation of synapses or repaire damaged synapses.
2 . The method of claim 1 , wherein the growth factor is brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), glial cell-line derived neurotrophic factor (GDNF), neurotrophin-3, neurotrophin-4, or any combination thereof.
3 . The method of claim 1 or claim 2 , wherein the growth factor is brain-derived neurotrophic factor (BDNF).
4 . The method of any one of claim 1 , wherein the auris-acceptable gel comprises a copolymer of polyoxyethylene and polyoxypropylene.
5 . The method of claim 4 , wherein the copolymer of polyoxyethylene and polyoxypropylene is poloxamer 407.
6 . The method of claim 1 , wherein the otic formulation comprises from about 15 wt % to about 17 wt % poloxamer 407.
7 . The method of claim 1 , wherein the otic formulation has an osmolarity from about 100 mOsm/L to about 1000 mOsm/L.
8 . The method of claim 1 , wherein the otic formulation has a pH from about 7.0 to about 8.0.
9 . The method of claim 1 , wherein the otic formulation comprises about 0.0001% to about 1% by weight of the growth factor.
10 . The method of claim 1 , wherein the otic formulation comprises between about 0.005% to about 0.5% by weight of the growth factor.
11 . The method of claim 1 , wherein the otic formulation provides sustained release of the growth factor over a period of at least 3 days.
12 . The method of claim 1 , wherein the growth factor is dissolved in the otic formulation.
13 . The method of claim 1 , wherein the otic formulation is administered through intratympanic injection.
14 . The method of claim 13 , wherein the otic formulation is deposited on or close to the round window membrane of the subject.
15 . The method of claim 1 , wherein the otic disease or condition is hearing loss or hearing impairment.
16 . The method of claim 1 , wherein the synapses-affecting event is selected from the group consisting of: head trauma, traumatic brain injury (TBI), acoustic trauma, cochlear implant surgery, sudden sensorineural hearing loss, drug-induced ototoxicity, and excitotoxicity.
17 . The method of claim 16 , wherein the drug-induced ototoxicity is chemotherapy-induced ototoxicity.
18 . The method of claim 16 , wherein the drug-induced ototoxicity is cisplatin-induced ototoxicity.
19 . The method of claim 16 , wherein the drug-induced ototoxicity is antibiotic-induced ototoxicity.
20 . The method of claim 1 , wherein the otic formulation repairs ribbon synapses.
21 . The method of claim 1 , wherein the otic formulation is administered within 7 days after onset of the synapses-damaging event.
22 . The method of claim 1 , wherein the otic formulation is administered within 3 days after onset of the synapses-damaging event.
23 . The method of claim 1 , wherein the otic formulation is administered within 1 day after onset of the synapses-damaging event.