AIM: To validate a novel sustained delivery system of liposome nanocarriers for inner-ear therapy and to investigate the transport pathway for their delivery. MATERIALS & 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. DISCUSSION: 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.
AIM: To validate a novel sustained delivery system of liposome nanocarriers for inner-ear therapy and to investigate the transport pathway for their delivery. MATERIALS & 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. DISCUSSION: 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.
Authors: Ildar I Sadreev; George W S Burwood; Samuel M Flaherty; Jongrae Kim; Ian J Russell; Timur I Abdullin; Andrei N Lukashkin Journal: Front Cell Neurosci Date: 2019-04-26 Impact factor: 5.505