Read by QxMD icon Read

Inner ear dexamethasone delivery

M Gehrke, J Verin, D Gnansia, G Tourrel, M Risoud, C Vincent, F Siepmann, J Siepmann
A new type of miniaturized implants for local controlled drug delivery to the inner ear is proposed: Hybrid Ear Cubes. They are composed of two main parts: (i) a cylinder, which is placed into a tiny hole (<0.4 mm) drilled into (or close to) the oval (or round) window, and (ii) a cuboid, which is placed into the middle ear. The drug is released at a pre-programmed rate into the perilymph: (i) via the cylindrical part of the implant, which is in direct contact with this liquid, and (ii) via diffusion from the cuboid through the oval/round window...
April 30, 2018: European Journal of Pharmaceutical Sciences
Keum-Jin Yang, Jihwan Son, So Young Jung, Gawon Yi, Jihye Yoo, Dong-Kee Kim, Heebeom Koo
To develop efficient carriers for inner ear drug delivery, we prepared four kinds of phospholipid-based nanoparticles: neutral, anionic, cationic, and cationic-PEG (polyethyleneglycol) particles. PEG was used to maintain long-term particle circulation in the perilymph, avoiding non-specific binding of particles to proteins. All four nanoparticles were about 200 nm in diameter, and their zeta potentials were -4.32, -26.0, +25.8, and -0.28, respectively, for neutral, anionic, cationic, and cationic-PEG nanoparticles...
April 16, 2018: Biomaterials
Alec N Salt, Stefan K Plontke
Local drug delivery to the ear has gained wide clinical acceptance, with the choice of drug and application protocol in humans largely empirically-derived. Here, we review the pharmacokinetics underlying local therapy of the ear using the drugs commonly used in clinical practice as examples. Based on molecular properties and perilymph measurements interpreted through computer simulations we now better understand the principles underlying entry and distribution of these and other drugs in the ear. From our analysis, we have determined that dexamethasone-phosphate, a pro-drug widely-used clinically, has molecular and pharmacokinetic properties that make it ill-suited for use as a local therapy for hearing disorders...
March 11, 2018: Hearing Research
Verena Scheper, Roland Hessler, Mareike Hütten, Maciej Wilk, Claude Jolly, Thomas Lenarz, Gerrit Paasche
Dexamethasone (DEX) can reduce fibrous tissue growth as well as loss of residual hearing which may occur after cochlear implantation. Little is known about the effect of local inner ear DEX treatment on the spiral ganglion neurons (SGN), which are the target of the electrical stimulation with a cochlear implant (CI). Three different clinically relevant strategies of DEX-delivery into the inner ear were used. DEX was either eluted from the electrode carriers' silicone, released from a reservoir by passive diffusion, or actively applied using a pump based system...
2017: PloS One
Jin Ho Lee, Se Heang Oh, Tae Ho Kim, Yoon Young Go, Jae-Jun Song
BACKGROUND: Dexamethasone (DEX) is used for the treatment of various inner ear diseases. However, the molecular mechanism of DEX on gentamicin induced hair cell damage is not known. Therefore, this study investigated the protective effect of DEX on gentamicin (GM)-induced ototoxicity and the effect of GM on the expression of apoptosis related genes. METHODS: The protective effects of DEX were measured by phalloidin staining of explant cultures of organ of Corti from postnatal day 2-3 mice with GM-induced hair cell loss...
2017: Biomaterials Research
S K Plontke, G Götze, T Rahne, A Liebau
Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (i. e., through intratympanic injection), intracochlear administration (particularly for gene and stem cell therapy), as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e...
January 2017: HNO
Ji Young Yoon, Keum-Jin Yang, Shi-Nae Park, Dong-Kee Kim, Jong-Duk Kim
Dexamethasone (Dex)-loaded PHEA-g-C18-Arg8 (PCA) nanoparticles (PCA/Dex) were developed for the delivery of genes to determine the synergistic effect of Dex on gene expression. The cationic PCA nanoparticles were self-assembled to create cationic micelles containing an octadecylamine (C18) core with Dex and an arginine 8 (Arg8) peptide shell for electrostatic complexation with nucleic acids (connexin 26 [Cx26] siRNA, green fluorescent protein [GFP] DNA or brain-derived neurotrophic factor [BDNF] pDNA). The PCA/Dex nanoparticles conjugated with Arg8, a cell-penetrating peptide that enhances permeability through a round window membrane in the inner ear for gene delivery, exhibited high uptake efficiency in HEI-OC1 cells...
2016: International Journal of Nanomedicine
S K Plontke, G Götze, T Rahne, A Liebau
Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (intratympanic injection); intracochlear administration, particularly for gene and stem cell therapy; as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e...
November 2016: HNO
Nezamoddin Berjis, Saeed Soheilipour, Alireza Musavi, Seyed Mostafa Hashemi
BACKGROUND: During the past years various drugs have been used for sudden sensorineural hearing loss (SSNHL) treatment including steroids that are shown to be beneficial. Directed delivery of high doses of steroids into the inner ear is suggested for its potential and known as intratympanic steroids therapy (IST). Despite the use of dexamethasone and methylprednisolone as the traditional treatments, there are still debates about the optimal dosage, preferred drug, and the route of administration...
2016: Advanced Biomedical Research
Douglas Sidell, Jonette A Ward, Angad Pordal, Carson Quimby, Michel Nassar, Daniel I Choo
OBJECTIVES: High dose antivirals have been shown to cause hearing loss when applied via the intratympanic route. The aim of this study was to determine if a combination therapy using dexamethasone (DXA) with either Cidofovir (CDV) or Ganciclovir (GCV), in solution or in PLGA-PEG-PLGA (PPP) hydrogel, is innocuous to the inner ear. METHODS: Cytomegalovirus (CMV)-free guinea pigs were separated into four principal study groups and treated via intratympanic injection (IT) of CDV/DXA solution, CDV/DXA Hydrogel, GCV/DXA solution and GCV/DXA hydrogel...
May 2016: International Journal of Pediatric Otorhinolaryngology
M Gehrke, J Sircoglou, D Gnansia, G Tourrel, J-F Willart, F Danede, E Lacante, C Vincent, F Siepmann, J Siepmann
A new type of advanced drug delivery systems is proposed: Miniaturized implants, which can be placed into tiny holes drilled into (or close to) the oval window. They consist of two parts: 1) A cylinder, which is inserted into the hole crossing the oval window. The cylinder (being longer than the depth of the hole) is partly located within the inner ear and surrounded by perilymph. This provides direct access to the target site, and at the same time assures implant fixation. 2) A cuboid, which is located in the middle ear, serving as a drug reservoir...
July 25, 2016: International Journal of Pharmaceutics
Dehong Yu, Changling Sun, Zhaozhu Zheng, Xueling Wang, Dongye Chen, Hao Wu, Xiaoqin Wang, Fuxin Shi
Minimally invasive delivery and sustained release of therapeutics to the inner ear are of importance to the medical treatment of inner ear disease. In this study, the injectable silk fibroin-polyethylene glycol (Silk-PEG) hydrogel was investigated as a drug delivery carrier to deliver poorly soluble micronized dexamethasone (mDEX) to the inner ear of guinea pigs. Encapsulation of mDEX with a loading up to 5% (w/v) did not significantly change the silk gelation time, and mDEX were evenly distributed in the PEG-Silk hydrogel as visualized by SEM...
April 30, 2016: International Journal of Pharmaceutics
Changling Sun, Xueling Wang, Dongye Chen, Xin Lin, Dehong Yu, Hao Wu
Ototoxicity is one of the most important adverse effects of cisplatin chemotherapy. As a common treatment of acute sensorineural hearing loss, systemic administration of steroids was demonstrated ineffective against cisplatin-induced hearing loss (CIHL) in published studies. The current study aimed to evaluate the potential protective effect of dexamethasone (DEX) encapsulated in polyethyleneglycol-coated polylactic acid (PEG-PLA) nanoparticles (DEX-NPs) against cisplatin-induced hearing loss following systemic administration...
April 21, 2016: Neuroscience Letters
Naila El Kechai, Elisabeth Mamelle, Yann Nguyen, Nicolas Huang, Valérie Nicolas, Pierre Chaminade, Stéphanie Yen-Nicolaÿ, Claire Gueutin, Benjamin Granger, Evelyne Ferrary, Florence Agnely, Amélie Bochot
The inner ear is one of the most challenging organs for drug delivery, mainly because of the blood-perilymph barrier. Therefore, local rather than systemic drug delivery methods are being developed for inner ear therapy. In this work, we have evaluated the benefit of a hyaluronic acid liposomal gel for sustained delivery of a corticoid to the inner ear after local injection into the middle ear in a guinea pig model. The liposomal gel was easily injectable as a result of the shear-thinning behavior of hyaluronic acid...
March 28, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
M Gehrke, J Sircoglou, C Vincent, J Siepmann, F Siepmann
Silicone-based drug delivery systems offer a great potential to improve the therapeutic efficacy and safety of a large variety of medical treatments, e.g. allowing for local long-term delivery of active agents to the inner ear. Different formulation parameters can be varied to adjust desired drug release kinetics. However, often only qualitative information is available on their effects, and product optimization is cumbersome. The aim of this study was to provide a quantitative analysis, allowing also for theoretical predictions of the impact of the device design on system performance...
March 2016: European Journal of Pharmaceutics and Biopharmaceutics
Julie Sircoglou, Maria Gehrke, Meryem Tardivel, Florence Siepmann, Juergen Siepmann, Christophe Vincent
HYPOTHESIS: The purpose of this study was to develop a new strategy to deliver drugs to the inner ear from dexamethasone (DXM)-loaded silicone implants and to evaluate the distribution of the drug in the cochlea with confocal microscopy. BACKGROUND: Systemic drug administration for the treatment of inner ear disorders is tricky because of the blood-cochlear barrier, a difficult anatomical access, the small size of the cochlea, and can cause significant adverse effects...
September 2015: Otology & Neurotology
Ya Liu, Claude Jolly, Susanne Braun, Thomas Stark, Elias Scherer, Stefan K Plontke, Jan Kiefer
Cochlear implants have been widely used for patients with profound hearing loss and partial deafness. Residual low-frequency hearing, however, may deteriorate due to insertion trauma and tissue response around the electrode array. The present study investigated in vitro and in vivo release of dexamethasone from silicone used for cochlear implant electrode carriers. The in vitro experiment involved an apparatus simulating the inner ear fluid environment in humans. Release from two sizes of silicone films (200 µm × 1 mm × 10 mm and 500 µm × 1 mm × 10 mm), each loaded with 2 % dexamethasone, and was measured for 24 weeks...
July 2016: European Archives of Oto-rhino-laryngology
Mareike Hütten, Anandhan Dhanasingh, Roland Hessler, Timo Stöver, Karl-Heinz Esser, Martin Möller, Thomas Lenarz, Claude Jolly, Jürgen Groll, Verena Scheper
Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo...
2014: PloS One
Stefan K Plontke, Alexander Glien, Torsten Rahne, Karsten Mäder, Alec N Salt
OBJECTIVE: To evaluate the feasibility and hearing outcome of a biocompatible degradable dexamethasone releasing implant for continuous drug delivery to the round window membrane in patients with idiopathic sudden sensorineural hearing loss (ISSHL) and insufficient recovery after systemic high dose glucocorticoid therapy. PATIENTS: Five patients with profound or moderate-to-severe hearing loss after systemic high-dose prednisolone for ISSHL received local salvage therapy with a controlled release dexamethasone implant in the middle ear...
August 2014: Otology & Neurotology
Laura Astolfi, Valeria Guaran, Nicola Marchetti, Elena Olivetto, Edi Simoni, Alberto Cavazzini, Claude Jolly, Alessandro Martini
Anti-inflammatory drugs can minimize the trauma and inflammation in the inner ear caused by cochlear implantation surgery. For this reason, much effort has recently been devoted to finding the best way to administer these anti-inflammatory drugs for a prolonged time and in a personalized dosage. One solution is constructing an electrode with a dispenser filled with anti-inflammatory drugs with a dosage adapted to suit each new cochlear implant user. The purpose of this study was to measure in vitro, by high-performance liquid chromatography-mass spectrometry assay, the amount of dexamethasone released in 78 days in a physiological solution by a filled dispenser...
February 2014: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"