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The aim of the present study was to evaluate the severity of vestibular drop attack (VDA) in Ménière's disease (MD) and to examine the association between VDA severity and other MD-related complaints. The study used a cross-sectional survey design using an electronic questionnaire. The mean age of participants was 56.7 years, and the mean duration of MD was 12.4 years. Four categories of VDA were identified based on level of severity. VDA occurred in 305 (50.7%) of the 602 patients. Of these, 133 patients (22%) experienced mild VDA (i.e., associated with tripping); 80 (13%) experienced moderate VDA (i.e., associated with fall threat unless they had been able to grab support); and 92 (15%) experienced severe VDA (i.e., patients fell to the ground, as in a classical Tumarkin attack). In 70%of participants, VDA occurred less than once a week. VDA lasted for only a few seconds in 90%of participants. 87%reported single attacks, whereas 13%experienced VDA in clusters. VDA was associated with visual auras, reduced quality of life, poor postural control, and fatigue. Approximately half of MD patients experience VDA with varying degrees of severity. If VDA causes falls or near-falls, the attacks should be appropriately treated.
BACKGROUND: The aim of the current study was to explore the associations among different therapeutic procedures, self-administered exercise, and characteristics of Ménière's disease. METHODS: The study used a retrospective design and included 539 people with Ménière's disease who were focusing on self-administered exercise. The mean age and history of Ménière's disease among these participants were 61.9 years and 15.6 years, respectively. Of the participants, 79.5% were female. The data were collected by an electronic questionnaire that focused on symptoms of Ménière's disease, exercise and training habits, balance problems, impacts of the complaints, quality of life, medical treatment, physiotherapy, and psychotherapy. RESULTS: Of the participants, 79.3% used medical treatment. Betahistine (56.8%) was the most popular followed by periodical anti-emetic use (41.0%) and diuretics (22.4%). Of the participants 70% were doing some self-administered training. The frequency of training depended on age, severity of balance problems, vestibular drop attacks, and gait problems. The type of training depended on age, quality of life, vestibular drop attacks, and gait problems. No association was found between vertigo and frequency/type of balance training. CONCLUSION: The use or effect of therapeutic procedures for Ménière's disease patients was not related to symptoms experienced. Most participants with Ménière's disease used training programs that aimed to alleviate their condition, especially balance-, gait-, and vestibular drop attack-associated problems. Patient support organizations should be working to help characterize the types of balance disorders people are dealing with in order to individually tailor a rehabilitation program to the patient's needs.
Silver nanoparticles (AgNPs) were shown to temporarily impair the biological barriers in the skin of the external ear canal, mucosa of the middle ear, and inner ear, causing partially reversible hearing loss after delivery into the middle ear. The current study aimed to elucidate the molecular mechanism, emphasizing the TLR signaling pathways in association with the potential recruitment of macrophages in the cochlea and the modulation of inflammation by ubiquitin-editing protein A20. Molecules potentially involved in these signaling pathways were thoroughly analysed using immunohistochemistry in the rat cochlea exposed to AgNPs at various concentrations through intratympanic injection. The results showed that 0.4 % AgNPs but not 0.02 % AgNPs upregulated the expressions of CD68, TLR4, MCP1, A20, and RNF11 in the strial basal cells, spiral ligament fibrocytes, and non-sensory supporting cells of Corti’s organ. 0.4 % AgNPs had no effect on CD44, TLR2, MCP2, Rac1, myosin light chain, VCAM1, Erk1/2, JNK, p38, IL-1β, TNF-α, TNFR1, TNFR2, IL-10, or TGF-β. This study suggested that AgNPs might confer macrophage-like functions on the strial basal cells and spiral ligament fibrocytes and enhance the immune activities of non-sensory supporting cells of Corti’s organ through the upregulation of CD68, which might be involved in TLR4 activation. A20 and RNF11 played roles in maintaining cochlear homeostasis via negative regulation of the expressions of inflammatory cytokines.
BACKGROUND: To examine whether the self-initiated exercise in Ménière’s disease fits the characteristics of the balance problems. METHODS: This retrospective study included 539 people with Ménière’s disease belonging to the Finnish Ménière Federation. The mean age was 61.9 years with a mean history of Ménière’s disease of 15.6 years. The data were collected with an online questionnaire. RESULTS: In total, 30% of the patients did not do any training, 23% did training once a week, 22% did 2-3 times a week, and 26% did the training daily. The most common training exercises were different self-training exercises (26%) followed by walking (16%), guided training (15%), viewing plus balance training (10%), and viewing training (4%). Non-defined balance problems (18%) were associated with recent vertigo attacks. Swaying type of balance problems were present in 23% and they used all types of training programs. Rocking type of balance disorder was present in 8% and they preferred guided training exercises. Tripping off type of balance disorder was present in 25% and they preferred viewing plus balance training. CONCLUSIONS: The type of self-training used was related to the type of balance problems reported. When choosing the vestibular rehabilitation in Ménière’s disease, the type of balance disorder should be characterized and the rehabilitation program should be individually tailored.
BACKGROUND: To explore and characterize balance problems in subjects with Ménière's disease (MD). METHODS: A total of 539 people with MD with a mean age of 61.9 years, mean disease history of 15.6 years, and 79.5% females were recruited. The online questionnaire, consisting of 39 questions, including both structured and open-ended questions, focused on symptoms of MD, balance problems, impacts of the complaints, and quality of life (QoL). RESULTS: After hearing loss (58%) and tinnitus (50%), balance problems (44%) were among the most commonly reported MD complaints, even higher than the impact of vertigo (40%). However, only 22% reported that those balance problems made obvious impacts in their daily lives. The most common balance problem that significantly reduced QoL was tripping (34%). Swaying (25%) had a limited impact on QoL, whereas rocking (10%) was less common but caused a significant impact on QoL. Non-defined balance problems were reported at 18%; these were occasional and correlated with vertigo attacks. Older participants had more frequent tripping problems. Younger participants more frequently reported swaying and rocking. CONCLUSIONS: Risk factors predicting poor postural control were mostly related to complaints reflecting otolith pathology. Different types of postural problems require different strategies to manage balance control and cope with the disease.
Background: The association between reporting adverse coronavirus disease 2019 (COVID-19) vaccination effects and those with a history of audiovestibular difficulties is unknown. The aim of this research is therefore to investigate adverse vaccination effects in adults with a history of Ménière's disease. Specifically, the incidence of adverse effects, the factors associated with those reporting adverse effects and the relationship between the reporting of audiovestibular and other adverse effects. Methods: A mixed-methods exploratory cross-sectional survey study design was used. Data were collected from 333 members of the Finnish Ménière Association. The survey was designed to obtain demographic information that may be associated with having adverse effects or not, vaccination-specific information and adverse vaccination effects. Both health and audiovestibular adverse events were identified. Data analysis included comparing those reporting and not reporting adverse vaccination effects. Results: The mean age was 63 years with 81% being female. Of the 327 respondents who had one of the COVID-19 vaccinations (Comirnatry/ Pfizer, Astra Zeneca, or Moderna), 203 (62%) reported no adverse effects. The type of or number of vaccinations were not related to the reporting of adverse effects. The most frequently reported adverse effects were injection site tenderness (38%), arm pain (21%), fever (15%) and headaches (15%). Post-vaccination tinnitus and vertigo (both 7%) were the most frequently reported audiovestibular-related symptoms, followed by aural fullness (6%) and hearing loss (4%). Those reporting previous pre-vaccination vertigo were more likely to have post-vaccination vertigo. The presence of post-vaccination tinnitus, hearing loss, and aural fullness, predicted the presence of post-vaccination vertigo. Conclusions: A small proportion of patients with a history of Ménière's disease may experience adverse post-vaccination effects. Further research is required to explore whether adverse post-vaccination audiovestibular effects are more prevalent in those with a history of otological disorders compared with the general population.
The study was aimed at evaluating the validity of impact measures among patients with Ménière's disease (MD) with outcome variables of EuroQol generic health-related quality of life (HRQoL) measures (i.e., EQ-5D) by using Visual Analogue Scale (VAS) and EQ-5D index values. 183 members (out of 200 contacted) of the Finish Ménière Association returned the questionnaires that they had filled out. Various open-ended and structured questionnaires focusing on diagnostic aspects of symptoms and impairment caused by the disease were used. For activity limitation and participation restriction, standardized questionnaires were used. Open-ended questions on impact of the disease were asked, and subsequently classified based on the WHO-ICF classification. The general HRQoL was evaluated with EQ-5D index value and EQ VAS instruments. Correlation and linear regression analyses were used to explore the association between HRQoL and other aspects. Based on the explanatory power of different models the disease specific semeionic model provides the most accurate prediction in EQ-5D index calculations (38 % of the variance explained). In EQ VAS scores, HRQoL is most accurately determined by participation restriction (53 % of the variance explained), but the worst prediction was in ICF-based limitations (8 % of the variance explained). Interestingly, attitude and personal trait explained the reduction of HRQoL somewhat better than ICF-based variables. Activity limitation and participation restrictions are significant components of MD, but are less frequently recognized as significant factors in self-evaluating the effect of MD on the quality of life. The current study results suggest that MD patients seem to have problem identifying factors causing activity limitation and participation restrictions and hence use the semiotic description focusing on complaints.
Background Silver nanoparticles (AgNPs) displayed strong activities in anti-bacterial, anti-viral, and anti-fungal studies and was reportedly efficient in treating otitis media .The potential impact of AgNPs on the inner ear was missing. Objective Attempted to evaluate the potential toxicity of AgNPs in the inner ear, middle ear, and external ear canal after transtympanic injection in rats. Results In in vitro studies, the IC50 for AgNPs in neutral red uptake assay was lower than that in NAD(P)H-dependent cellular oxidoreductase enzyme assay (WST-1) and higher than that in total cellular ATP and nuclear membrane integrity (propidium iodide) assessments. In in vivo experiments, magnetic resonance imaging (MRI) showed that significant changes in the permeability of biological barriers occurred in the middle ear mucosa, the skin of the external ear canal, and the inner ear at 5 h post-transtympanic injection of AgNPs at concentrations ranging from 20 μg/ml to 4000 μg/ml. The alterations in permeability showed a dosage-response relationship, and were reversible. The auditory brainstem response showed that 4000 μg/ml AgNPs induced hearing loss with partial recovery at 7 d, whereas 20 μg/ml caused reversible hearing loss. The functional change in auditory system was in line with the histology results. In general, the BALB/c 3T3 cell line is more than 1000 times more sensitive than the in vivo studies. Impairment of the mitochondrial function was indicated to be the mechanism of toxicity of AgNPs. Conclusion These results suggest that AgNPs caused significant, dose-dependent changes in the permeability of biological barriers in the middle ear mucosa, the skin of the external ear canal, and the inner ear. In general, the BALB/c 3T3 cell line is more than 1000 times more sensitive than the in vivo studies. The rat ear model might be expended to other engineered nanomaterials in nanotoxicology study.
Purpose: Intratympanic (IT) drug delivery receives attention due to its effectivity in treatment for Menière’s disease (MD). Due to the release of the consensuses and new evidence on IT drug delivery for MD have been published, the review with a view to supplementing the details of IT treatment of MD is indispensable. Methods: The literatures on IT injection for MD treatment over the last two decades are retrieved, International consensus (ICON) on treatment of Menière’s disease (2018), Clinical Practice Guideline (2020) and European Position statement on Diagnosis and Treatment of Meniere’s Disease (2018) are taken into account for reference, and follow advice from experts from Europe, USA and China. Results: Experts agree on the following: (1) The effectiveness of IT methylprednisolone (ITM) on vertigo control seems to be somewhat better than that of IT dexamethasone (ITD), and ITM can restore hearing in some cases. (2) Due to the ototoxicity of aminoglycosides, the application of intratympanic gentamicin (ITG) in MD patients with good hearing is conservative. However, some studies suggest that ITG with low doses has no significant effect on hearing, which needs to be further proved by clinical studies with high levels of evidence. (3) Currently, generally accepted treatment endpoint of ITG is no vertigo attack in a 12-month period or a vestibular loss in objective tests in the affected ear. Conclusion: More studies with high level of evidence are needed to evaluate the drug type, efficacy, and therapeutic endpoint of IT therapy for MD.
The etiology and underlying mechanism of Meniere's disease (MD) development are still unknown, although inflammation and autoimmunity have been implicated as underlying mechanisms. The human endolymphatic sac (ES) has been reported to have innate and adaptive immune capacity in local immune reactions. In vivo demonstration of inflammation of the ES in patients with MD is missing in the literature. We report the case of a 47-year-old female patient diagnosed with unilateral MD with genetic variants and cytokine markers indicating inflammation and vascular congestion of the ES. Endolymphatic hydrops in the right cochlea (grade 2) and vestibulum (grade 3) were detected using MRI. She carried heterozygous variants in MEFV (c.442G > C), IRF8 (c.1157G > T), ADA (c.445C > T), PEPD (c.151G > A), NBAS (c.4049T > C), CSF2RB (c.2222C > T), HPS6 (c.277G > T), IL2RB (c.1109C > T), IL12RB1 (c.1384G > T), IL17RC (c.260_271del GCAAGAGC TGGG), LIG1 (c.746G > A), RAG1 (c.650C > A), and SLX4 (c.1258G > C, c.5072A > G). In the serum, the levels of granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein 1α, and IL7 were significantly elevated, and the level of IL2Rα was reduced. Intratympanic administration of dexamethasone temporarily alleviated her hearing loss. Her vertigo was significantly relieved but remained slight after ES administration of corticosteroids.
BACKGROUND: Vestibular drop attacks (VDA), also called Tumarkin otolith crises as a complication of Ménière's disease (MD) were first described in 1936. Nevertheless, a clearer understanding of their prevalence and manifestations is needed. THE OBJECTIVE: of this review is to determine the frequency, correlates and consequences of VDA in MD. METHOD: Three databases were searched (i.e., MEDLINE, PubMed and Google Academia). A total of 1,791 references were identified, of which 18 studies were considered eligible. There was a large variation in the definition of VDA used in the studies. RESULTS: The frequency of VDA in MD leading to a fall to the ground varied from 3 to 19% in 9 hospital-based studies. In studies where a less restrictive definition of VDA included attacks with postural perturbation, tripping and near-to-fall situations was used the prevalence ranged from 50 to 72%. The pooled frequency of VDA leading to fall to the ground was 8% (95% CI 4 to 12%) in hospital-based studies. In these studies, VDA often occurred in severe and advanced MD whereas in cohort studies such connection was not found. Co-morbidity with migraine increased the likelihood of VDA occurrence in MD. In 3 studies syncope was recorded in connection to VDA with falls. In terms of clinical manifestation, audiometry, MRI, vestibular evoked muscle response measures indicated endolymphatic hydrops with involvement of the otolith system. The hearing loss was more pronounced, and balance was worse in MD patients with VDA than in those without. Injury associated with VDA was reported in only one study. CONCLUSIONS: VDA is a common phenomenon in MD, occurring even in mild MD and complicated with syncope. Some preliminary evidence suggests that VDA may lead to severe injuries.
Background: It is still challenging to detect endolymphatic hydrops (EH) in patients with Meniere’s disease (MD) using MRI. The aim of the present study was to optimize a sensitive technique generating strong contrast enhancement from minimum gadolinium–diethylenetriamine pentaacetic acid (Gd–DTPA) while reliably detecting EH in the inner ear, including the apex. Materials and methods: All imaging was performed using a 3.0 T MR system 24 h after intratympanic injection of low-dose Gd–DTPA. Heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed with magnitude and zero-filled interpolation (hT2W–FLAIR–ZFI) was optimized and validated in phantom studies and compared with medium inversion time inversion recovery imaging with magnitude reconstruction (MIIRMR). The following parameters were used in hT2W–FLAIR–ZFI: repetition time 14,000 ms, echo time 663 ms, inversion time 2900 ms, flip angle 120°, echo train length 271, and field of view 166 × 196 mm2. Results: MRI obtained using hT2W–FLAIR–MZFI yielded high-quality images with sharper and smoother borders between the endolymph and perilymph and a higher signal intensity ratio and more homogenous perilymph enhancement than those generated with MIIRMR (p < 0.01). There were predominantly grade II EHs in the cochleae and grade III EHs in the vestibule in definite MD. EH was detected in the apex of 11/16 ipsilateral ears, 3/16 contralateral ears in unilateral definite MD and 3/6 ears in bilateral MD. Conclusions: The novel hT2W–FLAIR–MZFI technique is sensitive and demonstrates strong and homogenous enhancement by minimum Gd–DTPA in the inner ear, including the apex, and yields high-quality images with sharp borders between the endolymph and perilymph.
Endolymphatic hydrops (EH) is considered the histological hallmark of Meniere's disease. Visualization of EH has been achieved by special sequences of inner ear magnetic resonance imaging (MRI) with a gadolinium-based contrast agent via intravenous or intratympanic administration. Although it has been applied for more than 10 years since 2007, a unified view on this technique has not yet been achieved. This paper presents an expert consensus on MRI of endolymphatic hydrops in the following aspects: indications and contra-indications for patient selection, methods of contrast-agent administration (intravenous or intratympanic), MRI sequence selection, the specific scanning parameter settings, and standard image evaluation methods and their advantages and disadvantages. For each part of this consensus, a comment is attached to elucidate the reasons for the recommendation.
The etiology and mechanism causing Meniere’s disease (MD) are not understood. The present study investigated the possible molecular mechanism of autoimmunity and autoinflammation associated with MD. Thirty-eight patients with definite MD and 39 normal volunteers were recruited, and 48 human cytokines/chemokines were quantified. In patients with MD pure tone audiograms, tympanograms and standard blood tests were performed. The mean hearing loss in the worse ear was 44.1 dB nHL. Compared to the referents, the concentrations of TNFα, IL1α, IL8, CTACK, MIP1α, MIP1β, G-CSF, and HGF in the sera of patients with MD were significantly elevated, while those of TRAIL and PDGFBB were significantly decreased. The area under the receiver operating characteristic curve (AUC) showed that G-CSF, MIP1α, and IL8 were above 0.8 and could be used to diagnose MD (p < 0.01), and the AUCs of CTACK and HGF were above 0.7 and acceptable to discriminate the MD group from the control group (p < 0.01). The revised AUCs (1 − AUC) of TRAIL and PDGFBB were above 0.7 and could also be used in the diagnosis of MD (p < 0.01). The linear regression showed significant correlations between MIP1α and GCSF, between IL2Rα and GCSF, between IL8 and HGF, between MIP1α and IL8, and between SCF and CTACK; there was a marginal linear association between IP10 and MIP1α. Linear regression also showed that there were significant age-related correlations of CTACK and MIG expression in the MD group (p < 0.01, ANOVA) but not in the control group. We hypothesize that G-CSF, IL8, and HGF, which are involved in the development of neutrophil extracellular traps (NETs) and through various mechanisms influence the functions of macrophages, lymphocytes, and dendritic cells, among others, are key players in the development of EH and MD and could be useful in elucidating the pathophysiological mechanisms leading to MD. Biomarkers identified in the present study may suggest that both autoimmune and autoinflammatory mechanisms are involved in MD. In the future, it will be valuable to develop a cost-effective method to detect G-CSF, IL8, HGF, CTACK, MIP1α, TRAIL, and PDGFBB in the serum of patient that have diagnostic relevance.
Background: The mechanisms of Meniere's disease (MD) remain largely unknown. The purpose of this study was to identify possible genetic variants associated with immune regulation in MD. Methods: The whole immune genome of 16 Chinese patients diagnosed with sporadic MD was sequenced using next-generation sequencing. Results: Definite pathological variants of MEFV (c.1223G>A, c.1105C>T), COL7A1 (c.5287C>T), and ADA (c.445C>T) contributing to the clinical phenotype were found in three patients. Limited and likely pathological variants of TLR3 (c.2228G>A) and RAB27A (c.560G>A) were detected in one patient each. The following definite pathological variants impairing the structure and function of translated proteins were detected in 10 patients, and multigene variants occurred in five patients: PRF1 (c.710C>A), UNC13D (c.1228A>C), COLEC11 (c.169C>T), RAG2 (c.200G>C), BLM (c.1937G>T), RNF31 (c.2533G>A), FAT4 (c.11498A>G), PEPD (c.788A>G), TNFSF12 (c.470G>A), VPS13B (c.11972A>T), TNFRSF13B (c.226G>A), ERCC6L2 (c.4613A>G), TLR3 (c.2228G>A), ADA (c.445C>T), PEPD (c.151G>A), and MOGS (c.2470G>A). The following limited pathological variants impairing the structure and function of translated proteins were detected in five patients, with double gene variants identified in one patient: EXTL3 (c.1396G>A), MTHFD1 (c.2057G>A), FANCA (c.2039T>C), LPIN2 (c.1814C>T), NBAS (c.4049T>C), and FCN3 (c.734G>A). Conclusion: Patients with sporadic MD carry multiple genetic variants involved in multiple steps of immune regulation, which might render patients susceptible to developing inflammation via both autoimmune and autoinflammation mechanisms upon internal stress.
An endosomal trap is a major barrier in gene therapy. We have designed an endosomolytic peptide based on the leucine zipper sequence and characterized it both structurally and functionally. The results illustrated that leucine zipper endosomolytic peptide (LZEP) exhibited appreciable hemolysis of human red blood cells (hRBCs) at pH 5.0, but negligible hemolysis at pH 7.4. Calcein release experiment indicated that only at pH 5.0 but not at pH 7.4, LZEP was able to permeabilize hRBCs. LZEP revealed significant self-assembly as well as peptide induced α-helical structure at pH 5.0. Unlike at pH 5.0, LZEP failed to self-assemble and showed a random coil structure at pH 7.4. Transfection data depicted that lipoplexes modified with LZEP resulted in significantly higher gene expression as compared to lipoplexes without LZEP. Interestingly, the transfection efficacy of LZEP modified lipid nanoparticles reached the levels of Lipofectamine 2000 (LF 2000), without any cellular toxicity as observed by MTT assay. The results suggest a novel approach for designing endosomolytic peptides by employing the leucine zipper sequence and simultaneously the designed peptides could be utilized for enhancing gene delivery into mammalian cells.
Background: Intratympanic administration of gadolinium chelate allows for a better visualization of endolymphatic hydrops (EH) using MRI than intravenous injection and was recently further improved to facilitate high-quality imaging of EH in 7 min. The aim of the present study was to simplify the intratympanic administration protocol by mixing gadolinium chelate with therapeutic dexamethasone and to evaluate the effects of this mixture on the visualization of EH in MRI. Materials and methods: In an in vitro study, the potential impact of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) on the stability of dexamethasone was evaluated by analyzing dynamic changes in dexamethasone with high-performance liquid chromatography (HPLC) after mixing with Gd-DTPA. Ten patients with definite Meniere's disease (MD) were recruited to study the potential interference of dexamethasone on MRI visualization of EH, and 49 patients with MD were recruited to evaluate the effect of intratympanic injection of Gd-DTPA mixed with dexamethasone on MRI of EH using a 3T MR machine and a novel heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed using a magnitude plus zero-filled interpolation (hT2FLAIR-MZFI) sequence. Results: The retention times and peak area of dexamethasone in HPLC were not modified by the addition of Gd-DTPA. EH grading in the cochlea and vestibule was not influenced in any ear by intratympanic injection of dexamethasone. Excellent inner ear images were obtained from all patients, and EHs with various grades were displayed. There were significant correlations between diagnosis and cochlear EH (p < 0.01, Spearman's Rho), between diagnosis and vestibular EH (p < 0.01, Spearman's Rho), and between cochlear and vestibular EH (p < 0.01, Spearman's Rho). The distribution of Gd-DTPA plus dexamethasone negatively correlated with the grade of vestibular EH. Injury of the endolymph-perilymph barrier was detected in one cochlea and three vestibules of 59 inner ears with MD. Conclusions: Intratympanic administration of Gd-DTPA plus dexamethasone yielded high-quality MRI images of EH in patients with MD using a novel 7-min protocol and simplified the clinical application. Intratympanic administration of Gd-DTPA plus dexamethasone might be used to test its therapeutic effect in future work. Level of evidence: 3.
Background Treatment 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. Results Measurements 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. Conclusion Novel 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.
Background Silver nanoparticles (Ag NPs) displayed strong activities in anti-bacterial, anti-viral, and anti-fungal studies and were reportedly efficient in treating otitis media. Information on distribution of AgNPs in different compartments of the ear is lacking. Objective To detect distribution of Ag NPs in the middle and inner ear and transportation pathways after transtympanic injection. Methods Contrast effect of Ag NPs in the micro CT imaging was assessed in a phantom. AgNPs at various concentrations (1.85 mM, 37.1 mM, and 370.7 mM) were administered to rat middle ear using transtympanic injection and cadaver heads were imaged using micro CT at several time points. Results The lowest concentration of Ag NPs that could be visualized using micro CT was 37.1 mM. No difference was observed between the solvents, deionized H2O and saline. Ag NPs at 37.1 mM were visible in the middle ear on 7 d post-administration. Ag NPs at 370.7 mM generated signals in the middle ear, ossicular chain, round window membrane, oval window, scala tympani, and Eustachian tube for both 4 h and 24 h time points. A gradient distribution of Ag NPs from the middle ear to the inner ear was detected. The pathways for Ag NPs to be transported from the middle ear into the inner ear are round and oval windows. Conclusion This study provided the imaging evidence that Ag NPs are able to access the inner ear in a dose-dependent manner after intratympanic administration, which is relevant to design the delivery concentration in the future clinic application in order to avoid adverse inner ear effect.