Name: trans-tympanic drug delivery for the treatment of ototoxicity
Uploaded: 2018-03-16T12:30:00
Description: Watch this Scientific Journal Video about Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity at JoVE.com

この資料で説明する作業は、NCI RO1 CA166907、NIDCD RO1 DC 002396 と RO3 DC011621 によって支持されました。

雄 Wistar ラットは、国立衛生研究所動物に従って処理されたガイドラインおよび南イリノイ大学学校の医学研究所動物ケアおよび使用委員会承認プロトコルを使用します。トランス鼓膜薬物送達の効果を検証する中薬管理および後 72 時間前に麻酔下でラットの聴性脳幹反応 (ABR) を行った
1. 聴性脳幹反応 (ABR)
注:ABR の測定は、聴覚テスト装...

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トランス鼓膜投与経路重要な全身性副作用全身投与する場合それ以外の場合になる蝸牛に薬や他のエージェントのローカライズされた配信できます。この投与法は、全身の経路を通じて達成されるとより有意に高い用量でアクションのサイトに薬の迅速なアクセスをできます。結果ここまで提示して公開以前ことを示したトランス鼓膜 [R] - N - フェニル イソプロピル アデノシン (R</...

聴覚末梢系は、シスプラチン、アミノグリコシド系抗生物質などの薬に絶妙に敏感です。さまざまな固形腫瘍、卵巣、精巣、ヘッドなどの治療に広く使用されている抗癌剤は、シスプラチンと頸部の癌。この薬の使用を経験した難聴は線量制限と1を扱う患者の 75-100% に影響を与える非常に一般的。カルボプラチン オキサリプラチンなどの他の薬をシスプラチン2,3,4、5、選択肢として浮上しているが、その有用性は、いくつかの癌に限られています。
初期の研究では、シスプラチン、アミノグリコシド系抗生物質による難聴を媒介に活性酸素種 (ROS) の重要な役割を示しています。その後の研究を示し、NADPH オキシダーゼの NOX3 アイソ フォーム、蝸牛の ROS のプライマリ ソースであるシスプラチン6,7をアクティブに。ROS 妥協の世代抗酸化につながる細胞の緩衝能力は8細胞膜の脂質過酸化反応を増加しました。また、シスプラチンは非常に有毒アルデヒド 4-ヒドロキシノネナール (4 HNE)、細胞死9,10のイニシエーターを生成するヒドロキシルラジカルの生産を増加します。これらの調査結果に基づいて、いくつかの抗酸化物質はシスプラチン難聴の治療のために検討されています。N - アセチルシステイン (NAC)、チオ硫酸ナトリウム (STS) や amifostine、D-メチオニンが含まれます。しかし、抗酸化療法の主要な心配はこれらの抗酸化物質がシスプラチンの抗酸化剤分子のチオール基との相互作用を通じて11を全身投与した場合シスプラチン化学療法有効性を減らすことができます。
抗酸化療法とこれらの問題の観点から本研究の目的は聴力損失を減らすために蝸牛に酸化防止剤と他の薬を提供するトランス鼓膜のルートを検討しました。特に有望な薬物と短い干渉 (si)、RNA、後述のトランス鼓膜のルートが表示されます。

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			<td height="19" style="height:19px;width:423px;">Ketathesia (100 mg/ml) 10 ml</td>
			<td style="width:192px;">Henry Schein</td>
			<td style="width:127px;">56344</td>
			<td style="width:284px;">Controlled substance&#160;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">AnaSed Injection/Xylazine (20 mg/ml) 20 ml</td>
			<td>Henry Schein</td>
			<td>33197</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">2.5 mm disposable ear specula</td>
			<td>Welch Allyn</td>
			<td>52432</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Surgical Scope</td>
			<td>Zeiss</td>
			<td></td>
			<td></td>
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		<tr height="19">
			<td height="19" style="height:19px;">29 G X 1/2 insulin syringe</td>
			<td>Fisher Scientific</td>
			<td>14-841-32&#160;</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">cis-Diammineplatinum(II) dichloride</td>
			<td>Sigma Aldrich</td>
			<td>P4394</td>
			<td>TOXIC - wear proper PPE</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Harvard 50-7103 Homeothermic Blanket Control Unit</td>
			<td>Harvard Apparatus</td>
			<td>Series 863</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Excel International 21 G X 3/4 butterfly needle</td>
			<td>Fisher</td>
			<td>14-840-34&#160;</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">BSP Single Speed Syringe Pump</td>
			<td>Brain Tree Sci, Inc</td>
			<td>BSP-99</td>
			<td></td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;">Pulse Sound Measurement System</td>
			<td>Bruel &#38; Kjaer</td>
			<td>Pulse 13 software</td>
			<td></td>
		</tr>
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			<td height="20" style="height:20px;">High-Frequency Module</td>
			<td>Bruel &#38; Kjaer</td>
			<td>3560C</td>
			<td></td>
		</tr>
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			<td height="19" style="height:19px;">1/8&#8243; Pressure-field Microphone &#8212;-Type 4138</td>
			<td>Bruel &#38; Kjaer</td>
			<td>bp2030</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">High Frequency Transducer</td>
			<td>Intelligent Hearing System</td>
			<td>M014600</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Opti-Amp Power Transmitter</td>
			<td>Intelligent Hearing System</td>
			<td>M013010P</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">SmartEP ABR System</td>
			<td>Intelligent Hearing System</td>
			<td>M011110</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Disposable Subdermal EEG Electrodes</td>
			<td>CareFusion</td>
			<td>019-409700</td>
			<td></td>
		</tr>
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			<td height="19" style="height:19px;">16% Formaldehyde, Methanol-free</td>
			<td>Fisher Scientific</td>
			<td>28908</td>
			<td>TOXIC - wear proper PPE&#160;</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">7 mL Borosilicate Glass Scintillation Vial</td>
			<td>Fisher Scientific</td>
			<td>03-337-26</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">EDTA</td>
			<td>Fisher Scientific</td>
			<td>BP118-500</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Sucrose</td>
			<td>Fisher Scientific</td>
			<td>S5-500</td>
			<td>Can be purchased through other vendors</td>
		</tr>
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			<td height="19" style="height:19px;">Tissue Plus OCT Compound</td>
			<td>Fisher Scientific</td>
			<td>4585</td>
			<td></td>
		</tr>
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			<td height="19" style="height:19px;">CryoMolds (15 mm x 15 mm x 5mm)</td>
			<td>Fisher Scientific</td>
			<td>22-363-553</td>
			<td>Can be purchased through other vendors</td>
		</tr>
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			<td height="19" style="height:19px;">Microscope Slides (25mm x 75mm)</td>
			<td>MidSci</td>
			<td>1354W</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Coverslips (22 x 22 x 1)</td>
			<td>Fisher Scientific</td>
			<td>12-542-B</td>
			<td>Can be purchased through other vendors</td>
		</tr>
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			<td height="19" style="height:19px;">Poly-L-Lysine Solution (0.01%)</td>
			<td>EMD Millipore</td>
			<td>A-005-C</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">HM525 NX Cryostat</td>
			<td>Thermo Fischer Scientific</td>
			<td>956640</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">MX35 Premier Disposable Low-Profile Microtome Blades</td>
			<td>Thermo Fischer Scientific</td>
			<td>3052835</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Wheaton&#8482;&#160;Glass 20-Slide Staining Dish with Removable Rack</td>
			<td>Fisher Scientific</td>
			<td>08-812</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Super Pap Pen Liquid Blocker</td>
			<td>Ted Pella, Inc.</td>
			<td>22309</td>
			<td></td>
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			<td height="19" style="height:19px;">Normal Donkey Serum</td>
			<td>Jackson Immuno Research</td>
			<td>017-000-121</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">TritonX-100</td>
			<td>Acros</td>
			<td>21568</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">BSA</td>
			<td>Sigma Aldrich</td>
			<td>A7906</td>
			<td>Can be purchased through other vendors</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Phospho-Stat1 (Ser727) antibody</td>
			<td>Cell Signaling</td>
			<td>9177</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">VR1 Antibody (C-15)</td>
			<td>Santa Cruz</td>
			<td>sc-12503</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">DyLight 488 Donkey anti Rabbit</td>
			<td>Jackson Immuno Research</td>
			<td>711-485-152</td>
			<td>Discontinued</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">DyLight 488 Donkey anti Goat</td>
			<td>Jackson Immuno Research</td>
			<td>705-485-003</td>
			<td>Discontinued</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">Rhodamine (TRTIC) Donkey anti Rabbit</td>
			<td>Jackson Immuno Research</td>
			<td>711-025-152</td>
			<td>Discontinued</td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">ProLong&#174; Diamond Antifade Mountant w/ DAPI</td>
			<td>Thermo Fisher</td>
			<td>P36971</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">(&#8722;)-N6-(2-Phenylisopropyl)adenosine</td>
			<td>Sigma Aldrich</td>
			<td>P4532</td>
			<td></td>
		</tr>
		<tr height="19">
			<td height="19" style="height:19px;">8-Cyclopentyl-1,3-dipropylxanthine</td>
			<td>Sigma Aldrich</td>
			<td>C101</td>
			<td></td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;">siRNA pSTAT1</td>
			<td>Qiagen</td>
			<td>Custome Made</td>
			<td>Kaur et al. 201120</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;">siRNA NOX3</td>
			<td>Qiagen</td>
			<td>Custome Made</td>
			<td>Kaur et al. 201120</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;">Scrambled Negative Control siRNA</td>
			<td>Qiagen</td>
			<td>1022076</td>
			<td>Kaur et al. 201120</td>
		</tr>
	</tbody>
</table>

trans-tympanic drug delivery for the treatment of ototoxicity

薬剤性難聴を治療するために保護剤の全身投与は、これらの保護剤が主な薬の化学療法の有効性と干渉する可能性可能性によって制限されます。これはその抗癌アクションは聴力損失に対して十分な保護を提供する抗酸化物質によって減衰は薬シスプラチンの特に当てはまります。他の現在か潜在的な otoprotective のエージェントは、全身投与する場合、同様の問題を引き起こす恐れが。限られた全身の副作用とローカルでこれらのエージェントの高いレベルの蝸牛に直接さまざまな生物学的製剤または保護剤のアプリケーションになります。本報告では、我々 は、蝸牛蝸牛に関する基礎科学研究を進めようと診療所で otoprotective エージェントの使用を指示する簡単な方法を提供するさまざまな薬や生物学的試薬の配信のトランス鼓膜メソッドを示します。このレポートは、トランス鼓膜薬物送達法の詳細をどのようにこの技術が正常に実験動物の治療に使用されてシスプラチン難聴の例を示します。

ABR 反応閾値の有意な上昇を示した次のシスプラチン投与 3 日間ラットを用いて測定します。トランス鼓膜 [R] - N - phenylisopropyladenosine 投与ラットにおけるこれらのしきい値の上昇を有意に減少した (R-ぴあ)、アデノシン1受容体アゴニスト15シスプラチンの前に。Rの作用の特異性-1受容体は、それが 8-シクロペンチル...

Watch this Scientific Journal Video about Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity at JoVE.com

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity

蝸牛にトランス鼓膜のルートを通じて医薬品の集中管理のための手法を提案します。この経路によるドラッグデリバリー シスプラチン化学療法剤の抗腫瘍効果と干渉しません。

難聴の治療のためのトランス鼓膜ドラッグデリバリー

The systemic administration of protective agents to treat drug-induced ototoxicity is limited by the possibility that these protective agents could ...

Research

JoVE Journal

Medicine

Thermal Ablation for the Treatment of Abdominal Tumors

腹部腫瘍の治療のための熱的アブレーション

Percutaneous thermal ablation is an emerging treatment option for many tumors of the abdomen not amenable to conventional treatments. During a thermal ...

Osmotic Drug Delivery to Ischemic Hindlimbs and Perfusion of Vasculature with Microfil for Micro-Computed Tomography Imaging

マイクロコンピュータ断層撮影イメージング用Microfilで虚血後肢と血管系の灌流に浸透ドラッグデリバリー

Preclinical research in animal models of peripheral arterial disease plays a vital role in testing the efficacy of therapeutic agents designed to ...

Heterotopic Mucosal Engrafting Procedure for Direct Drug Delivery to the Brain in Mice

マウスの脳に直接薬剤送達のための異粘膜移植手順

Delivery of therapeutics into the brain is impeded by the presence of the blood-brain barrier (BBB) which restricts the passage of polar and high ...

Slow-release Drug Delivery through Elvax 40W to the Rat Retina: Implications for the Treatment of Chronic Conditions

ラット網膜へのエルバックス40Wを通じて徐放性ドラッグデリバリー：慢性症状の治療のための含意

Diseases of the retina are difficult to treat as the retina lies deep within the eye. Invasive methods of drug delivery are often needed to treat these ...

Intraluminal Drug Delivery to the Mouse Arteriovenous Fistula Endothelium

マウスの動静脈瘻内皮への管腔内薬物送達

Delivery of therapeutic agents to enhance arteriovenous fistula (AVF) maturation can be administered either via intraluminal or external routes. The ...

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

薬剤耐性側頭葉てんかん患者における孔開存電極レコーディングのネットワーク解析

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control ...

Pancreatic Duct Infusion: An Effective and Selective Method of Drug and Viral Delivery

膵管注入:薬物およびウイルス送達の有効かつ選択的な方法

The pancreas is a bifunctional organ with both endocrine and exocrine components. A number of pathologies can afflict the pancreas, including diabetes, ...

Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients

Ivacaftor、主要な代謝産物および嚢胞性線維症患者の体液中の Lumacaftor の臨床サンプルの高スループット分析のための最適化された LC-MS/MS 法

Defects in the cystic fibrosis trans-membrane conductance regulator (CFTR) are the cause of cystic fibrosis (CF), a disease with life-threatening ...

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

Improved Method for the Establishment of an In Vitro Blood-Brain Barrier Model Based on Porcine Brain Endothelial Cells

体外血液脳関門ブタ脳血管内皮細胞に基づくモデルの確立のための改良法

The aim of this protocol presents an optimized procedure for the purification and cultivation of pBECs and to establish in vitro blood-brain barrier (BBB) ...

Novel Methods for Intranasal Administration Under Inhalation Anesthesia to Evaluate Nose-to-Brain Drug Delivery

鼻の頭脳への薬剤投与を評価する吸入麻酔下で経鼻投与する手法

Intranasal administration has been reported to be a potential pathway for nose-to-brain delivery of therapeutic agents that circumvents the blood-brain ...