A Novel Controlled Local Drug Delivery System for Inner Ear Disease

Paulson, David P.; Abuzeid, Waleed M.; Jiang, Hao; Oe, Tomoyuki; O’Malley, Bert W.; Li, Daqing

doi:10.1097/mlg.0b013e31815f8e41

Cited by 123 publications

(124 citation statements)

References 17 publications

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“…This may be achieved by injecting viscous gel formulations, or by placing wicks, microcatheters [35] into, or close to, the round window niche. Gel-based formulations include hyaluronates [36], collagens [37], chitosans [38], fibrins [39], starch, celluloses, 6 elatin [40], poloxamers [41], and many others. Viscosity that is too high may also result in the formation of an air bubble on the RWM, thus preventing effective diffusion, or may temporarily impair the ossicular mobility.…”

Section: Discussionmentioning

confidence: 99%

Intratympanic Injections: An Unsolved Mystery

Parelkar¹,

Thorawade²,

Jagade³

et al. 2015

IJOHNS

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Aims: The aim of this study was to test the effectiveness of intratympanic dexamethasone injections as a treatment for severe disabling tinnitus and also observe its effect on hearing loss if any. Materials and Methods: Thirty patients with severe disabling tinnitus in the age group 20 to 60 years were selected and randomly assigned to receive intratympanic injections of a dexamethasone solution 4 mg/ml (0.5 ml) or isotonic saline (0.5 ml) solution under topical anaesthesia, once per week for 4 weeks using a zero degree endoscope. Improvement in tinnitus was assessed using a visual analog scale, considering 2-point improvement as significant and alteration in hearing if any was noted by pure tone audiometery before and after the therapy. Results: The improvement in tinnitus was not significant, with no alteration in audiometery reports. Conclusions: Intratympanic therapy is an attractive mode of treatment because of its highly targeted delivery, low concentration of the drugs required and a very good patient tolerance. Although there has been no breakthrough in intratympanic therapy for tinnitus or other otological conditions, accessibility to the inner ear through the semipermeable round window membrane holds many promises in the near future.

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Section: Discussionmentioning

confidence: 99%

Intratympanic Injections: An Unsolved Mystery

Parelkar¹,

Thorawade²,

Jagade³

et al. 2015

IJOHNS

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“…The injected drug can be eliminated from the RW niche by the middle ear mucosa or through the Eustachian tube. 10 Thus, the perilymph drug level will be greatly affected by the presence of middle ear clearance. The higher viscosity of the NP colloidal suspension would prolong contact with the RWM and allow greater access to the inner ear, which will further increase the efficiency of drug delivery across the RWM.…”

Section: Time (H)mentioning

confidence: 99%

“…8 Local application onto the RWM is a promising way of targeting drugs to the structures of the inner ear, which can directly deliver chemotherapeutic agents into the inner ear, bypassing the BLB and avoiding systemic side effects. 9,10 It is noteworthy that single or repeated intratympanic injections of gentamicin 11 are now commonly used in the treatment of Ménière's Disease. In addition to aminoglycosides and anesthetics, a variety of drugs have been applied extracochlearly to the RW niche in humans, including neurotransmitters and neurotransmitter antagonists for tinnitus, steroids 12 and monoclonal antibodies for autoimmune inner ear disease, and apoptosis inhibitors (AM-111) for noise-induced hearing loss.…”

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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“…Types of sustained release formulations include liposomes, drug-loaded biodegradable microspheres and drug polymer conjugates, including gels [18,19,20,21,22]. Drug release from carrier systems may be driven only by the concentration gradient (such as for a drug in a resorbable gelatin sponge soaked with drug solution) or maintained by a gradual breakdown of the carrier, either spontaneously or induced by physical and chemical triggers (e.g.…”

Section: Pharmacokinetics Of the Inner Earmentioning

confidence: 99%

Principles of Local Drug Delivery to the Inner Ear

2009

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As more and more substances have been shown in preclinical studies to be capable of preventing damage to the inner ear from exposure to noise, ototoxic drugs, ischemia, infection, inflammation, mechanical trauma and other insults, it is becoming very important to develop feasible and safe methods for the targeted delivery of drugs to specific regions in the inner ear. Recently developed methods for sampling perilymph from the cochlea have overcome major technical problems that have distorted previous pharmacokinetic studies of the ear. These measurements show that drug distribution in perilymph is dominated by passive diffusion, resulting in large gradients along the cochlea when drugs are applied intratympanically. Therefore, in order to direct drugs to specific regions of the ear, a variety of delivery strategies are required. To target drugs to the basal cochlear turn and vestibular system while minimizing exposure of the apical cochlear turns, single one-shot intratympanic applications are effective. To increase the amount of drug reaching the apical cochlear turns, repeated intratympanic injections or controlled-release drug delivery systems, such as biodegradable biopolymers or catheters and pumps, are more effective. However, if the applied substance does not easily pass through the round window membrane, or if a more widespread distribution of drug in the ear is required, then intralabyrinthine injections of the substance may be required. Intralabyrinthine injection procedures, which are currently in development in animals, have not yet been proven safe enough for human use.

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A Novel Controlled Local Drug Delivery System for Inner Ear Disease

Abstract: We report the development of CGP-hydrogel, a biodegradable matrix that achieves local, sustained delivery of dexamethasone to the inner ear. There were no significant complications resulting from the surgical procedure or the administration of CGP-hydrogel to our murine model.

Cited by 123 publications

References 17 publications

Intratympanic Injections: An Unsolved Mystery

Intratympanic Injections: An Unsolved Mystery

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

Principles of Local Drug Delivery to the Inner Ear

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