Review of Round Window Membrane Permeability

Juhn, Steven K.; Hamaguchi, Yukihisa; Goycoolea, Marcos V.

doi:10.3109/00016488809138883

Cited by 87 publications

(93 citation statements)

References 10 publications

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“…The negative value (c) of the M W indicates that low M w drugs are more easily delivered through the RWM than high M w drugs are. Experimental studies have shown that low M w substances such as electrolytes, dye solution, and various kinds of antibiotics are easily transported through the RWM to the inner ear (Juhn et al, 1989). Studies also indicate that low M w substances are rapidly detected in the perilymph after intratympanic administration.…”

Section: Mathematical Model Fitting and Parameter Determinationmentioning

confidence: 94%

“…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%

“…It consists of three basic layers: an outer epithelium layer, a middle core of connective tissue, and an inner epithelium (Hellstrom et al, 1989). Animal studies have shown that this triple-layered membrane absorbs or secretes substances in the inner ear, which makes it the main portal for drug delivery to the inner ear (Juhn et al, 1989;Goycoolea & Lundman, 1997). For further development and translation of this promising therapeutic strategy to controlled clinical trials, it is necessary to conduct preclinical studies to establish pharmacokinetic and toxicological dose-effect relationships.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Mathematical Model Fitting and Parameter Determinationmentioning

confidence: 94%

Section: Analyzing Local Trans-rwm Drug Transport Profilesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…b) Insufficient dilution of lutein in DMSO. c) Loss of the agent through the Eustachian tube or by diffusion to the cochlear aqueduct d) Limitations to the diffusion of lutein through the round window membrane due to its high molecular weight (although large molecules can diffuse the round window membrane by pinocytosis) (Juhn et al, 1989). e) Early diffusion of lutein into the hair cells.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo effects of lutein against cisplatin-induced ototoxicity

Fidalgo

Saldaña²,

Trinidad

et al. 2016

Experimental and Toxicologic Pathology

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Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in: Experimental and Toxicologic Pathology 68.4 (2016): 197-204 A B S T R A C TIntroduction: Cisplatin is a commonly prescribed drug that produces ototoxicity as a side effect. Lutein is a carotenoid with antioxidant and anti-inflammatory properties previously tested for eye, heart and skin diseases but not evaluated to date in ear diseases.Aim: To evaluate the protective effects of lutein on HEI-OC1 auditory cell line and in a Wistar rat model of cisplatin ototoxicity.Materials and Methods: In vitro study: Culture HEI-OC1 cells were exposed to lutein (2.5-100 mM) and to 25 mM cisplatin for 24 h. In vivo study: Twenty eight female Wistar rats were randomized into three groups. Group A (n = 8) received intratympanic lutein (0.03 mL) (1 mg/mL) in the right ear and saline solution in the left one to determine the toxicity of lutein. Group B (n = 8) received also intraperitoneal cisplatin (10 mg/kg) to test the efficacy of lutein against cisplatin ototoxicity. Group C (n = 12) received intratympanic lutein (0.03 mL) (1 mg/mL) to quantify lutein in cochlear fluids (30 min,1 h and 5 days after treatment). Hearing function was evaluated by means of Auditory Steady-State Responses before the procedure and 5 days after (groups A and B). Morphological changes were studied by confocal laser scanning microscopy.Results: In vitro study: Lutein significantly reduced the cisplatin-induced cytotoxicity in the HEI-OC1 cells when they were pre-treated with lutein concentrations of 60 and 80 mM. In vivo study: Intratympaniclutein (1 mg/mL) application showed no ototoxic effects. However it did not achieve protective effect against cisplatin-induced ototoxicity in Wistar rats.Conclusions: Although lutein has shown beneficial effects in other pathologies, the present study only obtained protection against cisplatin ototoxicity in culture cells, but not in the in vivo model. The large molecule size, the low dose administered, and restriction to diffusion in the inner ear could account for this negative result

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“…The RWM is a membranous opening in the bone within the scala tympani that acts as a barrier to separate the PL from the middle ear space and only allows select substances to cross from the middle ear to the inner ear because of its relative permeability. 38,39 NPs readily cross the RWM. 20,21 In addition, the bioadhesive properties of the polymer may have contributed to the increased rate of absorption.…”

Section: Time (H)mentioning

confidence: 99%

Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration

Cai¹,

Wen²,

Wen³

et al. 2014

IJN

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In this paper, the potential of poly( d , l -lactide- co -glycolide acid) (PLGA) nanoparticles (NPs) for carrying single or compound drugs traversing the round window membrane (RWM) was examined after the round window (RW) administration of different NPs to guinea pigs. First, coumarin-6 was incorporated into PLGA NPs as a fluorescent probe to investigate its ability to cross the RWM. Then, PLGA NPs with salvianolic acid B (Sal B), tanshinone IIA (TS IIA), and total panax notoginsenoside (PNS) including notoginsenoside R 1 (R 1 ), ginsenoside Rg 1 (Rg 1 ), and ginsenoside Rb 1 (Rb 1 ) were developed to evaluate whether NPs loaded with compound drugs would pass through the RWM and improve the local bioavailability of these agents. PLGA NPs loaded with single or compound drugs were prepared by the emulsification solvent evaporation method, and their particle size distribution, particle morphology, and encapsulation efficiency were characterized. In vitro release study showed sustained-release profiles of Sal B, TS IIA, and PNS from the NPs. The pharmacokinetic results showed that NPs applied to the RWM significantly improved drug distribution within the inner ear. The AUC 0– t of coumarin-6 in the perilymph (PL) following RW administration of NPs was 4.7-fold higher than that of coumarin-6 solution, and the C max was 10.9-fold higher. Furthermore, the AUC 0– t of R 1 , Rg 1 , and Rb 1 were 4.0-, 3.1-, and 7.1-fold greater, respectively, after the application of NPs compared to the compound solution, and the C max were, respectively, 14.4-, 10.0-, and 16.7-fold higher. These findings suggest that PLGA NPs with unique properties at the nanoscale dimensions have a powerful ability to transport single or compound drugs into the PL through the RWM and remarkably enhance the local bioavailability of the encapsulated drugs in the inner ear. The use of PLGA NPs as nanoscale delivery vehicles to carry drugs across the RWM may be a promising strategy for the treatment of inner ear diseases.

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Review of Round Window Membrane Permeability

Cited by 87 publications

References 10 publications

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

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

In vitro and in vivo effects of lutein against cisplatin-induced ototoxicity

Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration

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