Pathway and morphological transformation of liposome nanocarriers after release from a novel sustained inner-ear delivery system.
OBJECTIVE
To validate a novel sustained delivery system of liposome nanocarriers for inner-ear therapy and to investigate the transport pathway for their delivery.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hearing & Balance Research Unit, Field of Otolaryngology, School of Medicine, University of Tampere, Tampere, Finland.
Jing
J
Zou
Rohit
R
Sood
Ya
Y
Zhang
Paavo K J
PK
Kinnunen
Ilmari
I
Pyykkö
D000818:Animals; D004337:Drug Carriers; D007758:Ear, Inner / Q000187:drug effects*; D008081:Liposomes; D049329:Nanostructures; D051381:Rats; D017207:Rats, Sprague-Dawley
D004337:Drug Carriers; D008081:Liposomes
MRI; animal; drug delivery; inner ear; liposome; minimally invasive technology; nanovector; osmotic pump; oval window; round window