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Middle ear application of a sodium hyaluronate gel loaded with neomycin in a Guinea pig model.

Abstract：

OBJECTIVE:Establishing methods for topical administration of drugs to the inner ear have great clinical relevance and potential even in a relatively short perspective. To evaluate the efficacy of sodium hyaluronate (HYA) as a vehicle for drugs that could be used for treatment of inner ear disorders. METHODS:The cochlear hair cell loss and round window membrane (RWM) morphology were investigated after topical application of neomycin and HYA into the middle ear. Sixty-five albino guinea pigs were used and divided into groups depending on the type of the treatment. Neomycin was chosen as tracer for drug release and pharmacodynamic effect. HYA loaded with 3 different concentrations of neomycin was injected to the middle ear cavity of guinea pigs. Phalloidin stained surface preparations of the organ of Corti were used to estimate hair cell loss induced by neomycin. The thickness of the midportion of the RWM was measured and compared with that of controls using light and electron microscopy. All animal procedures were pe rformed in accordance with the ethical standards of Karolinska Institutet. RESULT:Neomycin induced a considerable hair cell loss in guinea pigs receiving a middle ear injection of HYA loaded with the drug, demonstrating that neomycin was released from the gel and delivered to the inner ear. The resulting hair cell loss showed a clear dose-dependence. Only small differences in hair cell loss were noted between animals receiving neomycin solution and animals exposed to neomycin in HYA suggesting that the vehicle neither facilitated nor hindered drug transport between the middle ear cavity and the inner ear. One week after topical application, the thickness of the RWM had increased and was dependent upon the concentration of neomycin administered to the middle ear. At 4 weeks the thickness of the RWM had returned to normal. CONCLUSION:HYA is a safe vehicle for drugs aimed to pass into the inner ear through the RWM. Neomycin was released from HYA and transported into the inner ear as evidenced by hair cell loss.

journal_name

Ear Hear

journal_title

Ear and hearing

authors

Saber A,Laurell G,Bramer T,Edsman K,Engmér C,Ulfendahl M

doi

10.1097/AUD.0b013e31818ff98e

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

81-9

issue

eissn

0196-0202

issn

1538-4667

pii

00003446-200901000-00010

journal_volume

pub_type

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Middle ear application of a sodium hyaluronate gel loaded with neomycin in a Guinea pig model.