Drug delivery to the inner ear and methods of using same
The inventors have demonstrated that they can deliver therapeutic compositions to the inner ear of mammals via a variety of routes including the round window membrane, the semicircular canals, via cochleostomy and through the stapes footplate. Using pancaspase inhibitors, the inventors have shown that relatively large volumes of compositions can be injected with little to no hearing loss.
1. A method for delivering a pharmaceutical composition to the inner ear of a mammal without damaging hearing comprising the steps of:
a) visualizing the ear canal;
b) making an incision parallel to the annulus and elevating the tympanic membrane;
c) preserving and identifying the chorda tympani nerve;
d) visualizing the stapes footplate in the ear;
e) drilling a hole in the center of the stapes footplate with a diameter sufficiently large to allow the flow of perilymphatic fluid;
f) injecting about 0.25 μL-10.0 μL of a pharmaceutical composition for treatment of the inner ear of a mammal; and
g) filling the hole in the stapes footplate.
2. The method of claim 1 , wherein said pharmaceutical composition comprises an effective amount of adenoviral vector comprising a polynucleotide encoding for an anti-apoptotic polypeptide and a pancaspase inhibitor.
3. The method of claim 2 , wherein said adenoviral vector has E1/E3/E4 deletions.
4. The method of claim 2 , wherein said adenoviral vector comprises a promoter that regulates expression of said anti-apoptotic polypeptide.