Pathway and Morphological Transformation of Liposome Nanocarriers After Release From A Novel Sustained Inner-Ear Delivery System

Abstract

To validate a novel sustained delivery system of liposome nanocarriers for inner-ear therapy and to investigate the transport pathway for their delivery. Liposome nanocarriers containing gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (LPS+Gd-DOTA) were developed for MRI tracking the in vitro release profile and for in vivo uptake studies. Encapsulating Gd-DOTA did not modify the liposomes. The LPS+Gd-DOTA nanocarriers were slowly released from a miniature osmotic pump. The LPS+Gd-DOTA moved along the ossicular chain toward the oval window after an epitympanic injection, whereas they traveled directly to the round window after a mesotympanic injection. However, the round window membrane was the major pathway for the LPS+Gd-DOTA to enter the inner ear. LPS+Gd-DOTA were visualized on both sides of the cochlea within 6 days of in vivo delivery via the osmotic pump. The novel sustained inner-ear delivery system induced liposome nanocarriers into the inner ear efficiently without causing obvious adverse effect. There is the potential of using the system to administrate therapeutics in treating inner-ear diseases in the clinic.