Inner ear drug delivery through a cochlear implant: Pharmacokinetics in a Macaque experimental model

Manrique-Huarte, Raquel; Linera-Alperi, Marta Alvarez de; D, Parilli; Rodríguez, J.A.; Borro, Diego; Dueck, WF; Smyth, Daniel; Salt, Alec N.; Manrique, Manuel Jesús González

doi:10.1016/j.heares.2021.108228

Cited by 21 publications

(17 citation statements)

References 46 publications

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“…These agents are mainly glycocorticoids, which are administered locally or systemically [26][27][28]. A wide variety of systems are used to inhibit insertion trauma or to deliver drugs directly into the cochlea, such as intraoperative administration using catheters, longer-acting pump systems, or drug depots either in the silicone of the electrode array or in separate coatings [24][25][26][27][28][29][30][31][32][33][34]. The effect of polymer coatings without drug loading was tested by Hadler et al [29].…”

Section: Introductionmentioning

confidence: 99%

“…While drugs via catheters are administered as a bolus, pump systems steadily supply the cochlea over a longer period of time. However, pump cannula obstruction at low flow rates may occur, and microbiological control is required due to repeated transdermal refills [31]. In contrast, the drug depot is believed to be a safe method for cochlear application of corticosteroids [35,36] and reduces fibrosis in vivo [33].…”

Section: Introductionmentioning

confidence: 99%

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A PLLA Coating Does Not Affect the Insertion Pressure or Frictional Behavior of a CI Electrode Array at Higher Insertion Speeds

et al. 2022

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To prevent endocochlear insertion trauma, the development of drug delivery coatings in the field of CI electrodes has become an increasing focus of research. However, so far, the effect of a polymer coating of PLLA on the mechanical properties, such as the insertion pressure and friction of an electrode array, has not been investigated. In this study, the insertion pressure of a PLLA-coated, 31.5-mm long standard electrode array was examined during placement in a linear cochlear model. Additionally, the friction coefficients between a PLLA-coated electrode array and a tissue simulating the endocochlear lining were acquired. All data were obtained at different insertion speeds (0.1, 0.5, 1.0, 1.5, and 2.0 mm/s) and compared with those of an uncoated electrode array. It was shown that both the maximum insertion pressure generated in the linear model and the friction coefficient of the PLLA-coated electrode did not depend on the insertion speed. At higher insertion speeds above 1.0 mm/s, the insertion pressure (1.268 ± 0.032 mmHg) and the friction coefficient (0.40 ± 0.15) of the coated electrode array were similar to those of an uncoated array (1.252 ± 0.034 mmHg and 0.36 ± 0.15). The present study reveals that a PLLA coating on cochlear electrode arrays has a negligible effect on the electrode array insertion pressure and the friction when higher insertion speeds are used compared with an uncoated electrode array. Therefore, PLLA is a suitable material to be used as a coating for CI electrode arrays and can be considered for a potential drug delivery system.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A PLLA Coating Does Not Affect the Insertion Pressure or Frictional Behavior of a CI Electrode Array at Higher Insertion Speeds

et al. 2022

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“…Perilymph sample retrieved at 2, 24 h, and 7 days revealed a longitudinal gradient with higher drug concentration measured at the base compared to the apex, which persisted throughout the study period. This electrode-pump system was later studied in macaques with similar settings to measure the pharmacokinetic profile of FITC-Dextran (40 mg/ml, 2 μl/h) ( Manrique-Huarte et al, 2021 ). Results from this study revealed that similar drug concentrations from the base to apex in the perilymph was achieved within 2–24 h after infusion, and the uniform drug distribution was maintained for 7 days.…”

Section: Pharmacotherapy and Delivery Methodsmentioning

confidence: 99%

Inner Ear Drug Delivery for Sensorineural Hearing Loss: Current Challenges and Opportunities

Liu

Yang

2022

Front. Neurosci.

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Most therapies for treating sensorineural hearing loss are challenged by the delivery across multiple tissue barriers to the hard-to-access anatomical location of the inner ear. In this review, we will provide a recent update on various pharmacotherapy, gene therapy, and cell therapy approaches used in clinical and preclinical studies for the treatment of sensorineural hearing loss and approaches taken to overcome the drug delivery barriers in the ear. Small-molecule drugs for pharmacotherapy can be delivered via systemic or local delivery, where the blood-labyrinth barrier hinders the former and tissue barriers including the tympanic membrane, the round window membrane, and/or the oval window hinder the latter. Meanwhile, gene and cell therapies often require targeted delivery to the cochlea, which is currently achieved via intra-cochlear or intra-labyrinthine injection. To improve the stability of the biomacromolecules during treatment, e.g., RNAs, DNAs, proteins, additional packing vehicles are often required. To address the diverse range of biological barriers involved in inner ear drug delivery, each class of therapy and the intended therapeutic cargoes will be discussed in this review, in the context of delivery routes commonly used, delivery vehicles if required (e.g., viral and non-viral nanocarriers), and other strategies to improve drug permeation and sustained release (e.g., hydrogel, nanocarriers, permeation enhancers, and microfluidic systems). Overall, this review aims to capture the important advancements and key steps in the development of inner ear therapies and delivery strategies over the past two decades for the treatment and prophylaxis of sensorineural hearing loss.

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“…The method supposes passing a needle through either the round window or oval window and discharging the drug load into the cochlea or vestibule, respectively [ 58 ]. Alternatively, the drug can be released by a cochlear implant [ 64 , 65 , 66 , 67 ], osmotic mini-pumps [ 68 , 69 , 70 , 71 ], or through reciprocating perfusion systems [ 72 , 73 , 74 ]. This technique significantly increases drug bioavailability in the inner ear, having the highest efficiency among all administration possibilities [ 61 ].…”

Section: Administration Routesmentioning

confidence: 99%

Nanoparticles for the Treatment of Inner Ear Infections

et al. 2021

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The inner ear is sensitive to various infections of viral, bacterial, or fungal origin, which, if left untreated, may lead to hearing loss or progress through the temporal bone and cause intracranial infectious complications. Due to its isolated location, the inner ear is difficult to treat, imposing an acute need for improving current therapeutic approaches. A solution for enhancing antimicrobial treatment performance is the use of nanoparticles. Different inorganic, lipidic, and polymeric-based such particles have been designed, tested, and proven successful in the controlled delivery of medication, improving drug internalization by the targeted cells while reducing the systemic side effects. This paper makes a general presentation of common inner ear infections and therapeutics administration routes, further focusing on newly developed nanoparticle-mediated treatments.

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Inner ear drug delivery through a cochlear implant: Pharmacokinetics in a Macaque experimental model

Cited by 21 publications

References 46 publications

A PLLA Coating Does Not Affect the Insertion Pressure or Frictional Behavior of a CI Electrode Array at Higher Insertion Speeds

A PLLA Coating Does Not Affect the Insertion Pressure or Frictional Behavior of a CI Electrode Array at Higher Insertion Speeds

Inner Ear Drug Delivery for Sensorineural Hearing Loss: Current Challenges and Opportunities

Nanoparticles for the Treatment of Inner Ear Infections

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