Abstract
BackgroundTreatment of inner ear diseases remains a problem because of limited passage through the blood-inner ear barriers and lack of control with the delivery of treatment agents by intravenous or oral administration. As a minimally-invasive approach, intratympanic delivery of multifunctional nanoparticles (MFNPs) carrying genes or drugs to the inner ear is a future therapy for treating inner ear diseases, including sensorineural hearing loss (SNHL) and Meniere's disease. In an attempt to track the dynamics and distribution of nanoparticles in vivo, here we describe manufacturing MRI traceable liposome nanoparticles by encapsulating gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) (abbreviated as LPS+Gd-DOTA) and their distribution in the inner ear after either intratympanic or intracochlear administration.ResultsMeasurements of relaxivities (r1 and r2) showed that LPS+Gd-DOTA had efficient visible signal characteristics for MRI. In vivo studies demonstrated that LPS+Gd-DOTA with 130 nm size were efficiently taken up by the inner ear at 3 h after transtympanic injection and disappeared after 24 h. With intracochlear injection, LPS+Gd-DOTA were visualized to distribute throughout the inner ear, including the cochlea and vestibule with fast dynamics depending on the status of the perilymph circulation.ConclusionNovel LPS+Gd-DOTA were visible by MRI in the inner ear in vivo demonstrating transport from the middle ear to the inner ear and with dynamics that correlated to the status of the perilymph circulation.
Highlights
Treatment of inner ear diseases remains a problem because of limited passage through the bloodinner ear barriers and lack of control with the delivery of treatment agents by intravenous or oral administration
Nanoparticles dissociated by 5% sodium dodecyl sulfate (SDS) demonstrated T1 and T2 relaxation times similar to that of gadolinium-tetra-azacyclododecane-tetra-acetic acid (Gd-DOTA) with the same molar concentration of Gd (Table 1)
As the ratio of Gd chelate to lipid within the material was already maximized, an alternative strategy was pursued to enhance the r1 of the nanoparticles
Summary
Treatment of inner ear diseases remains a problem because of limited passage through the bloodinner ear barriers and lack of control with the delivery of treatment agents by intravenous or oral administration. As a minimally-invasive approach, intratympanic delivery of multifunctional nanoparticles (MFNPs) carrying genes or drugs to the inner ear is a future therapy for treating inner ear diseases, including sensorineural hearing loss (SNHL) and Meniere’s disease. One of the greatest challenges has been the limitations to passage through the blood-inner ear barriers and uncontrollable delivery of treatment agents after either intravenous or oral administration (Figure 1) [1]. Multifunctional nanoparticles (MFNPs) are a promising new means for the delivery of gene or drug to the inner ear for the treatment of inner ear diseases including sensorineural hearing loss (SNHL) and Meniere’s disease. The inner ear is composed of fluids, soft tissue, and bone [1] (Figure 1) This results in signal loss in histological study, which is incapable of retaining the inner ear fluids. It is inconvenient to observe the dynamics of MFNPs in the inner ear in histological studies
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