**4. Physiology**

Most of the structures of the cochlea are protected from the systemic circulation by the presence of a blood-cochlear barrier (or blood-labyrinthine barrier), similar to the bloodbrain barrier. There is exchange between the different compartments of the inner ear: between tympanic perilymph and vestibular perilymph and between endolymph and perilymph. But also between the inner ear fluids and cerebrospinal fluid and between the inner ear fluid and plasma (12) (13). Exchanges between endolymph and plasma are through the stria vascularis and between perilymph and plasma through the capillaries perilymphatic. At this level makes a pass filtering products: blood-labyrinthine barrier (13).

This blood–inner ear barrier consist of tight junctions and other mechanisms that limit access of molecules to inner ear targets. In fact the endothelial cells are connected with tight junctions and without fenestrations (14). This network of tightly coupled endothelial cells is the dominant component of the blood-cochlear barrier which make this solid barrier impermeable to macromolecules. In addition to this physical barrier, there is a chemical barrier between blood and endolymph/perilymph wich has a selectivity to electrolytes and water-soluble molecules (15).

In the fluid of the inner ear, there are other obstacles to the spread of drugs administered systemically: Because the scala media has a relatively high positive charge due to the endocochlear potential, the charge the drug carries will be a significant factor in its ability to enter the scala media, with positively charged drugs at a disadvantage (13).

The relatively high protein content of perilymph will tend to bind drugs (16). Protein interactions with drugs are as important in the perilymph as in blood. Albumin levels are high and can bind acidic drugs, and acid glycoproteins can bind basic drugs (16). Partition coefficients of drugs with these proteins will determine free concentration of the drug. The free fraction of the drug binds to the sensory cells and exerts its effect (13).

The cochlea is surrounded by the petrous bone. It was shown that there is a direct exchange between the extracellular space of the petrous bone and perilymph through the lacuna canaliculi which are canals or holes in the bone in free communication with the scala tympani (17).
