著者は、このプロジェクトの初期段階での技術支援のため専門家畜産と博士マルコA. Passini用ジョンマーストンに感謝します。この作品は、CLLの国立衛生研究所（; R01HD054413 R01NS41584）からの助成金によって賄われていた。

1。脳室内注入<ol><li>最初のステップは、注入ストック溶液の調製であり、これらのソリューションは、ウイルスベクター、プラスミドDNA、薬物、そして無菌条件下で注入されるべきです。 </li><li>注射部位の可視化のためにPBSでw / vのトリパンブルー0.05％ウイルスベクター（5-7μL合計）の所望の力価を混ぜる。 </li><li>プラスミドDNA溶液（5リットルμL合計）は、D -（+） - グルコース20％（w / v）の（1μL）、トリパンブルー（0.05％）PBS（1μL）、プラスミドを（〜5〜G /〜Lが含まれています）（2〜L）、および2.5 kDaの線形PEIホモポリマー（150 mM）の（1〜L）。 </li><li> 1〜2分のための低温麻酔を介してPND 2新生児を固定化する。 </li><li>この注射用針は、長い管を通って3ミリリットル3mLのハミルトンシリンジに接続されているマイクロリットルのキャリブレーション滅菌ガラスのマイクロピペットです。 </li><li>頭蓋骨に2mmの浸透のために調整するために針の先端を（スパチュラ付）ブレイク。注入溶液の入ったマイクロ遠心チューブに斜めに針を置きます。慎重に注射器のプランジャーを引いて、針に注射のソリューションを読み込みます。 </li><li>ソリューションの取り込み後に、チューブからシリンジを切り離し、さらにプランジャーを引き上げてから、再度針を取り付けます。 </li><li>親指と人​​差し指の間に右手の針を持ち、右手の手のひらに触れるプランジャーと中指、薬指の間に注射器を置きます。 </li><li>ガイドとして使用することができる、関連する解剖学的構造を照らすために光ファイバの光で左手と場所を使って頭の後ろの皮膚がしっかりと固定されたマウスをつかみます。 </li><li>場所矢状縫合の外側約0.25 mmおよび新生児の冠状縫合（ 図1A）の吻側0.50〜0.75ミリメートルで、頭蓋骨の表面に垂直に、深く針2mmの挿入し、の手のひらを使用してプランジャーを押し右手非常にゆっくりと慎重に。破裂血管や顔の腫れのために監視する。 </li><li>逆流を防ぐために、プランジャーの動きの中止後に針15秒を削除します。 </li><li>運動と一般的な応答性が復元されるまで回復するには、温めておいた容器に5〜10分間マウスを保つ。 </li></ol> 2。時間/顔面静脈を経由して静脈注射<ol><li>注入される溶液を調製し、濾過緑色食品色素で補足1:100希釈で、無菌条件下で注入する必要があります。 </li><li> 100μLガラスハミルトンシリンジの最後にルアー小さなプラスチックを取り付けます。ルアーに、33ゲージ0.25インチ皮下注射針を取り付けます。すべての部品がしっかりと接続されていることを保証する。 </li><li>容器への空気の注入は致命的であるようにシリンジ内に空気がないことを確認し、注入する量で注射器をロードする。それは多くの場合、ピペットパラフィルムの一部わたし注入されるボリュームに便利です。これにより、シリンジへの液の取り込みを明確に可視化することができます。 </li><li>ウィー視力のトランスは、簡単に新生児における浅側頭静脈、または顔面静脈、（図2A）を可視化するために使用されます。注射の前に、サージカルテープを使用してトランスに新生児を確保する。ガーゼは、動物の皮膚を損傷からテープを防ぐために、新生児とテープの間に配置する必要があります。テープは、呼吸を妨げないようにすること、その側のトランスに動物を固定します。新生児の首をやさしく顔面静脈が簡単に表示されるようにする必要があり、鼻は頭部を安定させるためにテープで固定してください。 </li><li>簡単に可視化を可能にするために2.25Xヘッドバンドの拡大鏡を使用して、徐々に静脈に針を挿入する。針が皮膚の下に表示したままにするので、静脈は非常に表面的です。 </li><li>ゆっくり静脈内に溶液の体積を吹き込む。緑色の染料は、注入の容易な視覚化することができます。 </li><li>完全にシリンジと極めて狭い針の穴のために残りの溶液の追放のプランジャーを押す間にタイムラグがあるので針を外す前に15秒を待ちます。 </li><li>針を除去した後、出血が停止するまで注射部位に圧力を適用するためにガーゼを使用してください。 </li><li>苦痛の徴候のための新生児を監視します。適切な注入後は、明白な苦痛は認めてはならない。新生児は、それがケージに戻される前に回復するために約5分間を与えられるべきである。 </li><li>針で血液がすぐに小口径のためにそれを目詰まりするので注射の間にPBSで針/注射器ユニットをフラッシュします。 </li></ol> 3。代表的な結果： ICV注入：脳は様々な時点注射後に収穫し、成功した注入技術を実証するために視覚化することができます。染料を注射液に添加されていない場合、それはでの精度をチェックすることは困難ですjection。心室のいずれかの適切な注入は、脳の注入側にトリパンブルーの配布が可能になります約10-15分のポスト噴射（ 図1B）。右と左大脳半球および嗅球の両方でトリパンブルーの均一な分布は、約60分の注射後（ 図1C）表示されます。これは、隣接する心室に青色色素の普及を許可する脳室の接続によるものです。正確な注射はまた、約12時間注入後（ 図1D）内の吻側、中央脊柱管に青い色素の分散可視化することができる。不正確な注射は、大脳半球の青色の欠如によって区別す​​ることができます。このケースでは、針の深さは十分ではなかったとされた注射液は、おそらく皮膚の下で配布されている。別の可能性は針、それによって心室と解決策が脳室の下に空に越えて渡して、脳にあまりにも深く浸透していることです。 IV注入：正確で効率的な時間的/顔面静脈注射は、注射の直後に視覚化することができます。解決策が注入されるように、緑色の色素が入ると顔面静脈（ 図2A）を流れる液の可視化が可能になります。さらに、マウスの改変された肌の色は、注射後に観察されます。新生児の正常なピンクの色は、注射液（ 図2B）における緑色食品色素の存在のために緑、に変換されます。新生児において観察された緑色の色の変化の程度は、使用する色素の濃度に依存している。注射のと練習期間中の単純な可視化のため、50倍希釈を推奨します。しかし、劇的に変化した肌のトーンは多くの場合、母親によって拒否される、したがって、染料または大幅に減少濃度の除去は、実験手順中に考慮すべき子犬をもたらす。不正確な注射は、注射の部位の皮膚の下に緑色の色素の蓄積になります。針の開口部が完全に静脈内に挿入されていない場合に発生する不完全な注射は、、いくつかのソリューションは、静脈を流れるときに見られると、一部は皮膚の下に蓄積されています。これが認められる場合は、針が血管にさらに挿入される必要があります。 <img src="/files/ftp_upload/2968/2968fig1.jpg" alt="図1"/> 図 PDN2マウスで成功したICV注射1。デモンストレーション。）心室にICV注射で利用される注射部位の模式図。ICVからの脳が左心室にPBSでトリパンブルーの仔注入B）、写真は15分にポスト噴射を撮影。C ICVから）脳は、左心室にPBSでトリパンブルーで子犬を注入、撮影した写真は、60分の注射後。D）吻側、中央脊柱管がICVに示されているが、左心室にPBSでトリパンブルーで子犬を注入、12時間注入後に撮影した写真。 <img src="/files/ftp_upload/2968/2968fig2.jpg" alt="図2"/> 子犬が非注入同腹と比較してPBSで緑の色素でIVを注入図 IV注射のために利用さ顔面静脈の2。PDN2マウスで成功したIV注射のデモンストレーション。）回路図は。B）、写真はすぐにポスト噴射を取ら。

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利害の衝突は宣言されません。

病気のマウスモデルを用いた研究は多くの場合、新生児に薬物または他の物質の投与を必要とします。このビデオでは、我々はステップバイCNSを標的とするために使用できる注射戦略の2つのタイプに関連するステップの手順を示す：脳室内（ICV）注射を利用したCNSに）直接注入を1;時間/をターゲット）、または2のIV注入顔面静脈。これらの注射のタイミングは非常に重要です。 ICV注射はフ?...

<table border="1"><tbody><tr><th>試薬の名前</th><th>会社</th><th>カタログ番号</th><th>コメント（省略可能） </th></tr><tr><td>緑の食用色素</td><td>マコーミック</td><td> N / A </td><td>フィルタ処理する必要があります</td></tr><tr><td>ハミルトンガラスシリンジ（100μL） </td><td>シグマAldrick </td><td> 20702 </td><td></td></tr><tr><td> LuerMxFスレッドスタイルホワイトナイロン</td><td>小さなパーツ、（株） </td><td> VPLF - LC78 - 1 - 25 </td><td></td></tr><tr><td>ファインゲージの注射針</td><td>ポッパー</td><td> 7111 </td><td>サイズ：33（SWG）× ¼&quot;（6.35 MM） </td></tr><tr><td>ウィー視力のトランス</td><td>レスピロニクス</td><td> 1017920 </td><td></td></tr><tr><td> 2.25Xヘッドバンド拡大鏡</td><td> MagEyes </td><td>モデル第5号</td><td>個々の好みに合わせて倍率を選択します。 </td></tr></tbody></table>

delivery of therapeutic agents through intracerebroventricular (icv) and intravenous (iv) injection in mice

血液脳関門は、脳をシールドで果たす保護的な役割にもかかわらず、それはどの神経変性疾患の1,2のために設計された潜在的な治療の失敗の最も頻繁にその結果中枢神経系（CNS）へのアクセスを制限します。このような脊髄性筋萎縮症（SMA）などの神経変性疾患は、下位運動ニューロンが影響される、CNSへの治療薬を導入するメリットは非常に大きくなります。このビデオの目的は、生後間もなく新生児マウスに治療材料を提供するために二つの異なる注入のパラダイムを示すことです。これらのいずれかの方法では、脳脊髄液3,4を介して中枢神経系への物質の配信で、その結果脳側脳室（脳室内）に直接注入される。第二の方法は、中枢神経系5を含む全身送達につながる、循環系にさまざまな治療法を導入することができる時間的な静脈注射（点滴）です。適切なウイルスベクターとウイルス血清型が利用される場合、CNSの広範な伝達が達成可能です。注射のための一時的な静脈の可視化と利用率は生後6日目まで可能です。納入材はCNSに到達することを意図されている場合、血液脳関門が原因で、その未熟な状況に、より透過性のある間しかし、これらの注射は、好ましくは、事前の生後2日目に、場所を取る必要があります。完全に開発された血液脳関門は、大幅に静脈内送達の有効性を制限する。手術の適性が達成されれば、両方の配信システムは、シンプルで効果的です。彼らはあらゆる広範な外科的装置を必要とせず、一人で行うことができます。しかし、これらの技術は課題がないわけではない。生後2日目子犬とそれに続く小さな対象地域の小さなサイズは、注射を行うことが困難と複製に最初に挑戦することができます。

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Delivery of Therapeutic Agents Through Intracerebroventricular ICV and Intravenous IV Injection in Mice

新生児マウスの中枢神経系への治療薬を導入する脳（脳室）と（静脈内）2）全身に1）：この記事では、注入の2つの非常に異なる方法を示しています。

マウスの脳室内（ICV）と静脈（IV）注入による治療薬のデリバリー

Despite the protective role that blood brain barrier plays in shielding the brain, it limits the access to the central nervous system (CNS) which most ...

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Delivery of Therapeutic Agents Through Intracerebroventricular (ICV) and Intravenous (IV) Injection in Mice

58.7K ビュー.  University of Missouri. 新生児マウスの中枢神経系への治療薬を導入する脳（脳室）と（静脈内）2）全身に1）：この記事では、注入の2つの非常に異なる方法を示しています。

ビデオ: Delivery of Therapeutic Agents Through Intracerebroventricular ICV and Intravenous IV Injection in Mice

Orthotopic Xenografting of Human Luciferase-Tagged Malignant Peripheral Nerve Sheath Tumor Cells for in vivo Testing of Candidate Therapeutic Agents

Although in vitro screens are essential for the initial identification of candidate therapeutic agents, a rigorous assessment of the drug's ability to inhibit tumor growth must be performed in a suitable animal model. The type of animal model that is best for this purpose is a topic of intense discussion. Some evidence indicates that preclinical trials examining drug effects on tumors arising in transgenic mice are more predictive of clinical outcome1and so candidate therapeutic agents are often tested in these models. Unfortunately, transgenic models are not available for many tumor types. Further, transgenic models often have other limitations such as concerns as to how well the mouse tumor models its human counterpart, incomplete penetrance of the tumor phenotype and an inability to predict when tumors will develop.
Consequently, many investigators use xenograft models (human tumor cells grafted into immunodeficient mice) for preclinical trials if appropriate transgenic tumor models are not available. Even if transgenic models are available, they are often partnered with xenograft models as the latter facilitate rapid determination of therapeutic ranges. Further, this partnership allows a comparison of the effectiveness of the agent in transgenic tumors and genuine human tumor cells. Historically, xenografting has often been performed by injecting tumor cells subcutaneously (ectopic xenografts). This technique is rapid and reproducible, relatively inexpensive and allows continuous quantitation of tumor growth during the therapeutic period2. However, the subcutaneous space is not the normal microenvironment for most neoplasms and so results obtained with ectopic xenografting can be misleading due to factors such as an absence of organ-specific expression of host tissue and tumor genes. It has thus been strongly recommended that ectopic grafting studies be replaced or complemented by studies in which human tumor cells are grafted into their tissue of origin (orthotopic xenografting)2. Unfortunately, implementation of this recommendation is often thwarted by the fact that orthotopic xenografting methodologies have not yet been developed for many tumor types.
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive sarcomas that occur sporadically or in association with neurofibromatosis type 13and most commonly arise in the sciatic nerve4. Here we describe a technically straightforward method in which firefly luciferase-tagged human MPNST cells are orthopically xenografted into the sciatic nerve of immunodeficient mice. Our approach to assessing the success of the grafting procedure in individual animals and subsequent non-biased randomization into study groups is also discussed.

Orthotopic Xenografting of Human Luciferase-Tagged Malignant Peripheral Nerve Sheath Tumor Cells for in vivo Testing of Candidate Therapeutic Agents

A method for reliably grafting luciferase-tagged human malignant peripheral nerve sheath tumor cells into the sciatic nerve of immunodeficient mice is described. The use of bioluminescence imaging to demonstrate proper establishment of tumor grafts and criteria for random segregation of animals into study groups are also discussed.

のために人間のルシフェラーゼ-タグ付き悪性末梢神経鞘腫瘍細胞の同所Xenografting in vivoで</em候補治療薬の>テスト

Although in vitro screens are essential for the initial identification of candidate therapeutic agents, a rigorous assessment of the drug's ability to ...

医学

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

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 diseases. Chronic retinal diseases such as retinal oedema or neovascularization usually require multiple intraocular injections to effectively treat the condition. However, the risks associated with these injections increase with repeated delivery of the drug. Therefore, alternative delivery methods need to be established in order to minimize the risks of reinjection. Several other investigations have developed methods to deliver drugs over extended time, through materials capable of releasing chemicals slowly into the eye. In this investigation, we outline the use of Elvax 40W, a copolymer resin, to act as a vehicle for drug delivery to the adult rat retina. The resin is made and loaded with the drug. The drug-resin complex is then implanted into the vitreous cavity, where it will slowly release the drug over time. This method was tested using 2-amino-4-phosphonobutyrate (APB), a glutamate analogue that blocks the light response of the retina. It was demonstrated that the APB was slowly released from the resin, and was able to block the retinal response by 7 days after implantation. This indicates that slow-release drug delivery using this copolymer resin is effective for treating the retina, and could be used therapeutically with further testing.

This paper details how Elvax 40W can be used as a slow-release method for drug delivery to the adult rat retina. The protocol for preparing, loading, and delivering the drug-resin complex to the eye is described.

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 ...

Ultrasound-guided Transthoracic Intramyocardial Injection in Mice

Murine models of cardiovascular disease are important for investigating pathophysiological mechanisms and exploring potential regenerative therapies. Experiments involving myocardial injection are currently performed by direct surgical access through a thoracotomy. While convenient when performed at the time of another experimental manipulation such as coronary artery ligation, the need for an invasive procedure for intramyocardial delivery limits potential experimental designs. With ever improving ultrasound resolution and advanced noninvasive imaging modalities, it is now feasible to routinely perform ultrasound-guided, percutaneous intramyocardial injection. This modality efficiently and reliably delivers agents to a targeted region of myocardium. Advantages of this technique include the avoidance of surgical morbidity, the facility to target regions of myocardium selectively under ultrasound guidance, and the opportunity to deliver injectate to the myocardium at multiple, predetermined time intervals. With practiced technique, complications from intramyocardial injection are rare, and mice quickly return to normal activity on recovery from anesthetic. Following the steps outlined in this protocol, the operator with basic echocardiography experience can quickly become competent in this versatile, minimally invasive technique.

Echocardiography-guided percutaneous intramyocardial injection represents an efficient, reliable, and targetable modality for the delivery of gene transfer agents or cells into the murine heart. Following the steps outlined in this protocol, the operator can quickly become competent in this versatile, minimally invasive technique.

マウスにおける超音波ガイド下経胸壁心筋内注射

Murine models of cardiovascular disease are important for investigating pathophysiological mechanisms and exploring potential regenerative therapies. ...

Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine

To date, many pharmacological agents used to treat or prevent arrhythmias in open-heart cases create undesired systemic side effects. For example, antiarrhythmic drugs administered intravenously can produce drops in systemic pressure in the already compromised cardiac patient. While performing open-heart procedures, surgeons will often either create a small port or form a pericardial cradle to create suitable fields for operation. This access yields opportunities for target pharmacological delivery (antiarrhythmic or ischemic preconditioning agents) directly to the myocardial tissue without undesired side effects.
We have developed a swine model for testing pharmacological agents for target delivery within the pericardial fluid. While fully anesthetized, each animal was instrumented with a Swan-Ganz catheter as well as left and right ventricle pressure catheters, and pacing leads were placed in the right atrial appendage and the right ventricle. A medial sternotomy was then performed and a pericardial access cradle was created; a plunge pacing lead was placed in the left atrial appendage and a bipolar pacing lead was placed in the left ventricle. Utilizing a programmer and a cardiac mapping system, the refractory period of the atrioventricular node (AVN), atria and ventricles was determined. In addition, atrial fibrillation (AF) induction was produced utilizing a Grass stimulator and time in AF was observed. These measurements were performed prior to treatment, as well as 30 min&#160;and 60 min&#160;after pericardial treatment. Additional time points were added for selected studies. The heart was then cardiopleged and reanimated in a four chamber working mode. Pressure measurements and function were recorded for 1 hr after reanimation. This treatment strategy model allowed us to observe the effects of pharmacological agents that may decrease the incidence of cardiac arrhythmias and/or ischemic damage, during and after open-heart surgery.

We have developed a swine model for the target delivery of pharmacological agents within the pericardial space/fluid. Using this approach, the relative benefits of administered agents on induced atrial fibrillation, relative refractory periods and/or ischemic protection can be investigated.

豚に心膜ターゲット・デリバリー・モデルでの薬剤の有効性をテストします

To date, many pharmacological agents used to treat or prevent arrhythmias in open-heart cases create undesired systemic side effects. For example, ...

Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals

Development of new therapeutic products requires efficacy testing in an animal model. The pulmonary route of administration can be utilized to deliver drugs locally and systemically. Evaluation of dry powder aerosols necessitates an efficient dispersion mechanism to maintain high concentrations in an exposure chamber or for direct endotracheal administration. While solutions exist to expose animals by passive inhalation to dry powder aerosols, most require masses of powder in large excess of the dose delivered. This precludes conducting early feasibility studies as insufficient drug is available at the research or early development stage to support the dose delivery requirements for conventional aerosol delivery systems. When designing an aerosol drug product, aerodynamic performance can relate directly to delivery efficiency and efficacy. Dispersion of powder into an aerosol requires energy input sufficient to overcome interparticulate forces, and particle engineering approaches can substantially improve aerosol performance. We have developed a dispersion system (dosator) which can aerosolize engineered dry powder aerosols efficiently for the purpose of direct pulmonary insufflation, dispersion into an exposure system or generation for analytical purposes.

During development of drugs for pulmonary delivery, it is necessary to evaluate pharmacokinetics and efficacy in an animal model. We present a method to build a disposable aerosol dispersion system from of-the-shelf components that can be used to administer intrapulmonary dry powder aerosol to rodents.

小動物への治療薬の肺内吸入のための使い捨てDosators

Development of new therapeutic products requires efficacy testing in an animal model. The pulmonary route of administration can be utilized to deliver ...

Intranasal Delivery of Therapeutic Stem Cells to Glioblastoma in a Mouse Model

The intrinsic tropism towards brain malignancies renders stem cells as promising carriers of therapeutic agents against malignant tumors. The delivery of therapeutic stem cells via the intranasal route is a recently discovered alternative strategy, with strong potential for clinical translation, due to its non-invasive nature compared to intracranial implantation or delivery via systemic routes. The lack of blood brain barrier further strengthens the therapeutic potential of stem cells undergoing intranasal brain entry. This article summarizes the essential techniques utilized in our studies and outlines the basic principles of intranasal strategy for stem cell delivery using a mouse model of intracranial glioma xenografts. We demonstrate the optimized procedures that generate consistent and reproducible results with specific predetermined experimental parameters and offer guidelines for streamlined work flow that ensure efficient execution and reliable experimental outcome. The article is designed to serve as a baseline for further experimental customization based on hypothesis, stem cell types, or tumor specifics.

Stem cells are promising therapeutic carriers to treat brain tumors due to their intrinsic tumor tropism. Non-invasive intranasal stem cell delivery bypasses the blood brain barrier and demonstrates strong potential for clinical translation. This article summarizes the basic principles of intranasal stem cell delivery in a mouse model of glioma.

マウスモデルにおける膠芽細胞腫に対する治療用幹細胞の鼻腔内送達

The intrinsic tropism towards brain malignancies renders stem cells as promising carriers of therapeutic agents against malignant tumors. The delivery of ...

A Rat Carotid Artery Pressure-Controlled Segmental Balloon Injury with Periadventitial Therapeutic Application

Cardiovascular disease remains the leading cause of death and disability worldwide, in part due to atherosclerosis. Atherosclerotic plaque narrows the luminal surface area in arteries thereby reducing adequate blood flow to organs and distal tissues. Clinically, revascularization procedures such as balloon angioplasty with or without stent placement aim to restore blood flow. Although these procedures reestablish blood flow by reducing plaque burden, they damage the vessel wall, which initiates the arterial healing response. The prolonged healing response causes arterial restenosis, or re-narrowing, ultimately limiting the long-term success of these revascularization procedures. Therefore, preclinical animal models are integral for analyzing the pathophysiological mechanisms driving restenosis, and provide the opportunity to test novel therapeutic strategies. Murine models are cheaper and easier to operate on than large animal models. Balloon or wire injury are the two commonly accepted injury modalities used in murine models. Balloon injury models in particular mimic the clinical angioplasty procedure and cause adequate damage to the artery for the development of restenosis. Herein we describe the surgical details for performing and histologically analyzing the modified, pressure-controlled rat carotid artery balloon injury model. Additionally, this protocol highlights how local periadventitial application of therapeutics can be used to inhibit neointimal hyperplasia. Lastly, we present light sheet fluorescence microscopy as a novel approach for imaging and visualizing the arterial injury in three-dimensions.

The rat carotid artery balloon injury mimics the clinical angioplasty procedure performed to restore blood flow in atherosclerotic vessels. This model induces the arterial injury response by distending the arterial wall, and denuding the intimal layer of endothelial cells, ultimately causing remodeling and an intimal hyperplastic response.

過期治療アプリケーションを用いてラット頸動脈圧制御区分バルーン損傷

Cardiovascular disease remains the leading cause of death and disability worldwide, in part due to atherosclerosis. Atherosclerotic plaque narrows the ...

Intratracheal Administration of Dry Powder Formulation in Mice

In the development of inhalable dry powder formulations, it is essential to evaluate their biological activities in preclinical animal models. This paper introduces a noninvasive method of intratracheal delivery of dry powder formulation in mice. A dry powder loading device that consists of a 200 &#181;L gel loading pipette tip connected to an 1 mL syringe via a three-way stopcock is presented. A small amount of dry powder (1-2 mg) is loaded into the pipette tip and dispersed by 0.6 mL of air in the syringe. Because pipette tips are disposable and inexpensive, different dry powder formulations can be loaded into different tips in advance. Various formulations can be evaluated in the same animal experiment without device cleaning and dose refilling, thereby saving time and eliminating the risk of cross-contamination from residual powder. The extent of powder dispersion can be inspected by the amount of powder remaining in the pipette tip. A protocol of intubation in mouse with a custom-made light source and a guiding cannula is included. Proper intubation is one of the key factors that influences the intratracheal delivery of dry powder formulation to the deep lung region of the mouse.

Dry powder formulations for inhalation have great potential in treating respiratory diseases. Before entering human studies, it is necessary to evaluate the efficacy of the dry powder formulation in preclinical studies. A simple and noninvasive method of the administration of dry powder in mice through the intratracheal route is presented.

マウスにおける乾燥粉末製剤の気管内投与

In the development of inhalable dry powder formulations, it is essential to evaluate their biological activities in preclinical animal models. This paper ...

Liujunzi煎じ薬:UC-CRC予防のための効果的な治療法

Establishment of Coloproctitis Cancer Model in Mice and Evaluation of Therapeutic Effect of Chinese Medicine

Colorectal cancer (CRC) is a common malignancy of the digestive system and has become the third most common malignancy worldwide and the second leading cause of malignancy-related death. Ulcerative coloproctitis (UC) is a precancerous lesion, and UC-associated CRC (UC-CRC) is the most common subtype of CRC. Therefore, a reasonable UC-CRC model is the cornerstone and guarantee of new drug development. Traditional Chinese medicine (TCM) has been widely used in the treatment of UC-CRC due to its good efficacy. As a classic tonic prescription of TCM, Liujunzi decoction (LJZD) has been widely used in the treatment of UC-CRC. In this study, a UC-CRC model was established by combining azomethane and dextran sulfate sodium, and the LJZD was administered. The data confirmed that LJZD can effectively inhibit cancer transition in UC-CRC by using mouse body weight, colorectal length, pathological and inflammatory factors, colorectal barrier function, and cancer markers. This protocol provides a system for evaluating the efficacy of TCM in the prevention and treatment of UC-CRC.

著者スポットライト:大腸がんに対する伝統的な中国の治療法としてのLiujunzi煎じ薬

This protocol provides a mouse model of ulcerative coloproctitis-associated colorectal cancer induced by azomethane combined with dextran sulfate sodium. The model was used to evaluate the efficacy of traditional Chinese medicine compounds in the prevention and treatment of colorectal cancer.

マウスにおける大腸肛門炎モデルの設定と漢方薬の治療効果評価

Colorectal cancer (CRC) is a common malignancy of the digestive system and has become the third most common malignancy worldwide and the second leading ...