Recent advances in local drug delivery to the inner ear

Kechai, Naila El; Agnely, Florence; Mamelle, Elisabeth; Nguyen, Yann; Ferrary, Évelyne; Bochot, Amélie

doi:10.1016/j.ijpharm.2015.08.015

Cited by 137 publications

(123 citation statements)

References 176 publications

(132 reference statements)

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“…Advances in the field of cochlear implants have significantly improved speech reception abilities in these individuals. More recently, cochlear implant based drug delivery systems have been garnering much interest as a potential modality of treatment, e.g., for reduction of inflammation and tissue reaction to the implant, and to improve auditory nerve survival (Aliuos et al, 2016; Ayoob et al, 2015; El Kechai et al, 2015; Gillespie et al, 2015; Lee et al, 2015; Rivera et al, 2012). Once inserted, the presence of the CI electrode within the scala tympani, which is connected to the cerebrospinal fluid of the subarachnoid space via the cochlear aqueduct (Gopen et al, 1997), may limit the specific drugs that can be utilized and also may comprise an increased risk of infection, e.g., meningitis.…”

Section: Discussionmentioning

confidence: 99%

Effects of brain-derived neurotrophic factor (BDNF) on the cochlear nucleus in cats deafened as neonates

2016

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Many previous studies have shown significant neurotrophic effects of intracochlear delivery of BDNF in preventing degeneration of cochlear spiral ganglion (SG) neurons after deafness in rodents and our laboratory has shown similar results in developing cats deafened prior to hearing onset. This study examined the morphology of the cochlear nucleus (CN) in a group of neonatally deafened cats from a previous study in which infusion of BDNF elicited a significant improvement in survival of the SG neurons. Five cats were deafened by systemic injections of neomycin sulfate (60mg/kg, SQ, SID) starting one day after birth, and continuing for 16–18 days until auditory brainstem response (ABR) testing demonstrated profound bilateral hearing loss. The animals were implanted unilaterally at about 1 month of age using custom-designed electrodes with a drug-delivery cannula connected to an osmotic pump. BDNF (94μg/ml; 0.25μl/hr) was delivered for 10 weeks. The animals were euthanized and studied at 14–23 weeks of age. Consistent with the neurotrophic effects of BDNF on SG survival, the total CN volume in these animals was significantly larger on the BDNF-treated side than on the contralateral side. However, total CN volume, both ipsi- and contralateral to the implants in these deafened juvenile animals, was markedly smaller than the CN in normal adult animals, reflecting the severe effects of deafness on the central auditory system during development. Data from the individual major CN subdivisions (DCN, Dorsal Cochlear Nucleus; PVCN, Posteroventral Cochlear Nucleus; AVCN, Anteroventral Cochlear Nucleus) also were analyzed. A significant difference was observed between the BDNF-treated and control sides only in the AVCN. Measurements of the cross-sectional areas of spherical cells showed that cells were significantly larger in the AVCN ipsilateral to the implant than on the contralateral side. Further, the numerical density of spherical cells was significantly lower in the AVCN ipsilateral to the implant than on the contralateral side, consistent with the larger AVCN volume observed with BDNF treatment. Together, findings indicate significant neurotrophic effects of intracochlear BDNF infusion on the developing CN.

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Section: Discussionmentioning

confidence: 99%

Effects of brain-derived neurotrophic factor (BDNF) on the cochlear nucleus in cats deafened as neonates

2016

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“…The RWM acts like a semipermeable membranous interfaces (Duan & Chen, 2009;Liu et al, 2013;El Kechai et al, 2015) and low-molecular weight substances such as various kinds of aminoglycoside antibiotics and corticosteroids are rapidly transported through it (Juhn et al, 1989). Passive diffusion was generally considered to be the main mechanism by which drug migrates from the middle ear cavity to the inner ear through the triple-layered RWM (Salt & Plontke, 2005).…”

Section: Analyzing Local Trans-rwm Drug Transport Profilesmentioning

confidence: 99%

“…Topical administration may be achieved by either the intratympanic or intracochlear routes. However, intracochlear administration not only requires complex surgical techniques, but also carries significant risks such as possible histological damages, infection, and toxicity (Staecker et al, 2010;El Kechai et al, 2015;Kim et al, 2015). In contrast, intratympanic administration, which was introduced in clinics more than half a century ago, has proven to be an effective route for inner ear drug delivery with minimum damages (Duan & Chen, 2009).…”

Section: Introductionmentioning

confidence: 99%

Mathematical modeling for local trans-round window membrane drug transport in the inner ear

Zhang

Wen

et al. 2016

Drug Delivery

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(2016) Mathematical modeling for local trans-round window membrane drug transport in the inner ear, Drug Delivery, 23:8, 3082-3087, DOI: 10.3109/10717544.2016 AbstractThe structure and composition of the round window membrane (RWM) make it a particularly effective pathway for drug delivery to the inner ear. Therefore, predicting the efficiency of RWM transport would provide useful information for enhancing local application. In the present study, a mathematical model was established to achieve this goal. A series of drugs with different physicochemical properties were introduced in the inner ear cavity of guinea pigs via RWM by intratympanic application. The perilymphatic drug concentration (C) data were used to calculate the permeability coefficient (K p ) of different drugs diffusing through the RWM. The experimental data were fitted using the Matlab software to set up the numerical model based on Fick's diffusion law and the single-compartment model following extravascular administration, which facilitated the prediction of the permeation profiles of different drugs while trans-RWM. In summary, this mathematical model is a contribution toward developing potentially useful RWM administration simulating tools.

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“…Эти же его свойства не позволяют ксенобиотикам (лекарственным веществам) проницать во внутрикохле-арные структуры и оказывать ототропные эффекты. Пассивное прохождение высокомолекулярных, водорас-творимых и заряженных молекул при таких условиях крайне низко [21]. Однако есть наблюдения о транспорте через ГЛБ дисперсных частиц.…”

Section: Introductionunclassified

“…При этом очевидно, что он будет зависеть от способа инкор-порации ДТС (внутривенное введение, местное интра-тимпанальное, транстубарное, эндоауральное). Помимо размера, другими важными нанофармакологическими ха-рактеристиками наночастиц-носителей рассматривают-ся: форма, морфология, химический состав, зарядовое состояние поверхности [21,23], оптимальные параметры которых для осуществления доступа ко внутреннему уху также остаются открытыми.…”

Section: Introductionunclassified

Пористый Кремний Как Наноматериал Для Дисперсных Транспортных Систем Направленной Лекарственной Доставки Ко Внутреннему Уху

Спивак¹,

Белорус²,

Паневин³

et al. 2018

Журнал Технической Физики

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Recent advances in local drug delivery to the inner ear

Cited by 137 publications

References 176 publications

Effects of brain-derived neurotrophic factor (BDNF) on the cochlear nucleus in cats deafened as neonates

Effects of brain-derived neurotrophic factor (BDNF) on the cochlear nucleus in cats deafened as neonates

Mathematical modeling for local trans-round window membrane drug transport in the inner ear

Пористый Кремний Как Наноматериал Для Дисперсных Транспортных Систем Направленной Лекарственной Доставки Ко Внутреннему Уху

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