Drug Delivery to the Cochlea Using PLGA Nanoparticles

Tamura, Tetsuya; Kita, Tomoko; Nakagawa, Takayuki; Endo, Tamao; Kim, Taesoo; Ishihara, Tsutomu; Mizushima, Yutaka; Higaki, Megumu; Ito, Juichi

doi:10.1097/01.mlg.0000180174.81036.5a

Cited by 113 publications

(75 citation statements)

References 13 publications

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“…183 Furthermore, recent work had demonstrated that systemic application of PLGA nanoparticles loaded with rhodamine resulted in the appearance of NPs in the liver, cochlea, and kidney, however, the placement of NPs into the RMW caused substantially higher accumulation of rhodamine in the scala tympani. 184 Another study had shown a wide distribution of PLGA throughout all turns of chinchilla cochlea when NPs were placed upon the RWM for a duration of 40 minutes. 185 Although delivery of BDNF to the inner ear using NPs has not been studied yet, either for systemic or for intratympanic administration, we assume that PLGA nanoparticles are a very promising approach for the inner ear drug targeting.…”

Section: Nanoparticulate Deliverymentioning

confidence: 99%

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Khalin¹,

Alyautdin²,

Kocherga³

et al. 2015

IJN

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Neurodegenerative causes of blindness and deafness possess a major challenge in their clinical management as proper treatment guidelines have not yet been found. Brain-derived neurotrophic factor (BDNF) has been established as a promising therapy against neurodegenerative disorders including hearing and visual loss. Unfortunately, the blood–retinal barrier and blood–cochlear barrier, which have a comparable structure to the blood–brain barrier prevent molecules of larger sizes (such as BDNF) from exiting the circulation and reaching the targeted cells. Anatomical features of the eye and ear allow use of local administration, bypassing histo-hematic barriers. This paper focuses on highlighting a variety of strategies proposed for the local administration of the BDNF, like direct delivery, viral gene therapy, and cell-based therapy, which have been shown to successfully improve development, survival, and function of spiral and retinal ganglion cells. The similarities and controversies for BDNF treatment of posterior eye diseases and inner ear diseases have been analyzed and compared. In this review, we also focus on the possibility of translation of this knowledge into clinical practice. And finally, we suggest that using nanoparticulate drug-delivery systems may substantially contribute to the development of clinically viable techniques for BDNF delivery into the cochlea or posterior eye segment, which, ultimately, can lead to a long-term or permanent rescue of auditory and optic neurons from degeneration.

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Section: Nanoparticulate Deliverymentioning

confidence: 99%

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Khalin¹,

Alyautdin²,

Kocherga³

et al. 2015

IJN

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“…Higher perilymphatic drug concentrations have been detected in many laboratories after delivering the drugs intratympanically through the intact RWM compared with other routes, such as the peritoneum and bloodstream. The molecules used for studies of RWM delivery include antibiotics, poly(lacticglycolic acid) (PLGA), methylprednisolone, and so on (Tamura et al, 2005;Bird et al, 2007;Plontke et al, 2007). The intact RWM approach (intratympanic pathway) may provide higher a perilymphatic concentration of exogenous molecules with low drug dosage by bypassing the bloodlabyrinth barrier.…”

Section: Routes Of Administration For Inner Ear Gene Therapymentioning

confidence: 99%

Current Status and Prospects of Gene Therapy for the Inner Ear

2011

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Inner ear diseases are common and often result in hearing disability. Sensorineural hearing loss is the main cause of hearing disability. So far, no effective treatment is available although some patients may benefit from a hearing aid equipped with a hearing amplifier or from cochlear implantation. Inner ear gene therapy has become an emerging field of study for the treatment of hearing disability. Numerous new discoveries and tremendous advances have been made in inner ear gene therapy including gene vectors, routes of administration, and therapeutic genes and targets. Gene therapy may become a treatment option for inner ear diseases in the near future. In this review, we summarize the current state of inner ear gene therapy including gene vectors, delivery routes, and therapeutic genes and targets by examining and analyzing publications on inner ear gene therapy from the literature and patent documents, and identify promising patents, novel techniques, and vital research projects. We also discuss the progress and prospects of inner ear gene therapy, the advances and shortcomings, with possible solutions in this field of research.

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“…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. 40 NPs deposited locally in the middle ear cavity could be transported by pinocytosis through the RWM, and then enter the perilymph through lymphatic and blood vessels.…”

Section: Time (H)mentioning

confidence: 99%

“…PLGA NPs encapsulating rhodamine, a red fluorescent dye, placed on the RWM were detected in the scala tympani. 20 Similarly, iron oxide-loaded PLGA NPs applied to the RWM were found in the cochlea with or without exposure to magnetic forces. 21 PLGA NPs loaded with multiple agents and applied to the RWM have scarcely been reported.…”

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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Drug Delivery to the Cochlea Using PLGA Nanoparticles

Abstract: These findings indicate that PLGA nanoparticles can be an useful drug carrier to the cochlea via local application.

Cited by 113 publications

References 13 publications

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

Current Status and Prospects of Gene Therapy for the Inner Ear

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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