Local drug delivery to the entire cochlea without breaching its boundaries

Abstract

SUMMARYThe mammalian cochlea is one of the least accessible organs for drug delivery. Systemic administration of many drugs is severely limited by the blood-labyrinth barrier. Local intratympanic administration into the middle ear would be a preferable option in this case and the only option for many old and newly emerging classes of drugs but it leads to base-to-apex drug concentration gradients that are orders of magnitude and well outside the therapeutic windows. Here we present an efficient, quick, reliable and simple method of cochlear pumping, through large amplitude, low-frequency reciprocal oscillations of the stapes and round window that can consistently and uniformly deliver drugs along the entire length of the intact cochlea within minutes without disrupting cochlear boundaries. The method should facilitate novel ways of approaching the treatment of inner ear disorders since we have overcome the challenge of delivering of therapeutics along the entire length of the cochlea. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/838508v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@a1753org.highwire.dtl.DTLVardef@816d0aorg.highwire.dtl.DTLVardef@11de641org.highwire.dtl.DTLVardef@1f7bd27_HPS_FORMAT_FIGEXP M_FIG C_FIG