Yazarlar, bay Ray Lee, Bay HC Leung ve Bay Wallace So'ya ışık kaynağı ve toz oytucusu yapma konusundaki nazik yardımları için teşekkür etmek istiyor; ve hayvan görüntüleme yardımı için Fakülte Çekirdek Tesisi. Çalışma, Hong Kong Araştırma Hibe Konseyi (17300319) tarafından desteklendi.

Bu çalışmada yapılan deneyler, Hong Kong Üniversitesi Öğretim ve Araştırma için Canlı Hayvanların Kullanımı Komitesi (CULATR) tarafından onaylanmıştır. Luciferaz messenger RNA'nın (mRNA), %5 sentetik peptit PEG12KL4'ünü ve mannitolün %94,5'ini (w/w) içeren sprey dondurma kurutma (SFD) ile hazırlanan kuru toz formülasyonları akciğerde mRNA ekspresyonunun16. SFD tozunun kütle ortanca aerodinamik çapı (MMAD) 2,4 μm'dir. Sprey kurutulmuş (SD) mannitol tozu, toz dağılımında kullanılan hava hacminin etkisini araştırmak için kullanılır16. SD tozunun MMAD'si 1,5 μm'dir.
1. Kuru toz insufflator imalatı ve kuru tozun yüklenmesi
<ol><li>(İsteğe bağlı) Kuru tozun statik yüklerini (bir şişede) ve 200 μL filtresiz yuvarlak jel yükleme pipet ucunu nötralize edin. Üreticinin talimatına göre anti-statik bir top veya deiyonizasyon işlevine sahip bir terazi kullanın.</li>
	<li>Yaklaşık 4 cm x 4 cm büyüklüğünde bir tartım kağıdı hazırlayın. Kağıdı çapraz olarak ikiye katlayın ve açın.</li>
	<li>Tartım kağıdında 1-2 mg kuru toz ağırlığındadır.</li>
	<li>Jel yükleme pipet ucunu ucun daha geniş açıklığı boyunca tozla doldurun. Toz, ucun dar ucuna yakın gevşek aglomeralar oluşturana kadar tozu paketlemek için hafifçe dokunun (Şekil 1A). Toz dağılımını engelleyebileceğinden tozu çok sıkı paketlemekten kaçının.</li>
	<li>Toz yüklü ucu üç yönlü bir stopcock aracılığıyla 1 mL şırındıya bağlayın (Şekil 1B). Şırındın boyutu tozu dağıtmak için kullanılan hava hacmine göre değiştirilebilir. Tozun dökülmesini önlemek için bağlantı sırasında ucu ve şırınnayı dikey olarak tutun. Uygulama hemen yapılmazsa, ucun açıklıklarını kapatmak için parafilm kullanın ve idareye kadar geçici olarak uygun durumda saklayın.</li>
</ol>2. Entübasyon cihazının imalatı
<ol><li>Işık kaynağı (Şekil 2)<ol>
<li>Işık yayan diyot (LED) torcu ve 0,8-1 mm çapında esnek bir optik fiber ile özel yapım bir ışık kaynağı hazırlayın.</li>
		<li>Led torcunun net lensine bir el matkabı veya matkap ucu ile ortalanmış bir delik yapın, böylece optik fiber zar zor geçebilir.</li>
		<li>Optik fiberi delikten geçirin. Optik fiberin diğer ucundaki maksimum parlaklık için yerleştirmenin konumunu ve derinliğini ayarlamak için LED torcu kapatın.</li>
		<li>Optik fiberi net epoksi tutkal ile yerine yapıştırın.</li>
	</ol>
</li>
	<li>Kılavuzak canül (Şekil 3)<ol>
<li>1 mL plastik Pasteur pipet (Şekil 3A) alın ve pipeti her iki ucunda tutun.</li>
		<li>Pipet ortasını alevin 5-10 cm üzerine yerleştirerek ısıtmak için bir alkol lambası (veya Bunsen brülörü gibi laboratuvardaki diğer ısı kaynakları) kullanın (Şekil 3B). Pipetleri eşit şekilde ısıtıldığından emin olmak için döndürün.</li>
		<li>Plastik yumuşak ve deforme olduğunda, pipeti alevden uzaklaştırın ve pipeti hafifçe uzatın.</li>
		<li>Ortadaki gerilmiş pipetleri bir çift makasla A ve Bölüm B'ye kesin (Şekil 3C-E). Bölüm A'yı ince uç pipet, Bölüm B'yi ise yol gösterici bir kaval kemiği olarak kullanın. Kılavuz ampul ile başarılı entübasyon şansını artırmak için, Bölüm B'nin sonunda(Şekil 3F)bir eğim yapın (hayvanın yaralanma riskini artırabilecek çok keskin değil). Kılavuz kanüle 200 μL jel yükleme pipet ucu (toz yükleme için) yerleştirildiğinde, kanülü 1-2 mm çıkıntı yapmalıdır. NOT: Entübasyon için uygun boyuta (iç ve dış çap) sahip kılavuz bir kanül (Bölüm B), içine 21 kalibrelik bir iğne sığabilirken, 17 kalibrelik bir iğnenin içine de sığabilir. Uygun boyuta ulaşmak için pipetlerin gerilmesinde birden fazla girişim gerekebilir.</li>
		<li>(İsteğe bağlı): Optik fiberi tutmanın daha kolay olması için daha esnek hale getirmek için kılavuz kolayın geniş ucunda küçük bir açıklık kesin (Şekil 3F). Bu açıklık ayrıca sıvı aerosolun yönetimi için bir mikrosprayer takılmasına izin verir.</li>
	</ol>
</li>
</ol>3. Entübasyon
<ol><li>Fareyi (BALB/c, 7-9 hafta) ketamin (100 mg/kg) ve ksilazin (10 mg/kg) ile intraperitoneal enjeksiyonla uyuşturun.</li>
	<li>Pleksiglastan yapılmış bir platform hazırlayın ve bir kelepçe ile bir standa monte etmenin (Şekil 4A). Anestezi edilmiş fareyi platforma (yaklaşık 60° eğimde) bir destek pozisyonunda yerleştirin. Platformun eğim yüksekliği ve açısı, standın üzerindeki kelepçenin konumuna göre ayarlanabilir.</li>
	<li>Kesici dişlerini naylon bir diş ipi üzerine bağlayarak fareyi askıya alın (Şekil 4B). Farenin konumunu bir bant parçası veya lastik bantla sabitleyin.</li>
	<li>Optik fiberi, kılavuz kanülün açılmasıyla fiber seviyesinin ucuyla entübasyondan önce kılavuz kanüle yerleştirin. Aydınlatmak için LED torcu açın.</li>
	<li>Nefes nefese bırakmak için farenin dilini bir çift asa ile hafifçe çıkıntılayın.</li>
	<li>Diğer yandan, içinde optik fiber olan kılavuzlu canülleri tutmak için kullanın. Ağız boşluğundan yerleştirin. Optik fiberden gelen aydınlatma ile nefes borusunun açılması ses telleri arasında bir delik olarak görselleştirilebilir.</li>
	<li>Kılavuz canüllerin eğimini açıklığın orta çizgisine doğru hizalayın (Şekil 5A). Trakeal açıklığındaki canülün en iyi ucunu hedef alarak kılavuzlu kanolü optik fiberle nefes borusuna hafifçe entübe edin.</li>
	<li>Entübasyon üzerine, optik fiberi hızla çıkarın ve kılavuz damarı nefes borusunun içinde bırakın (Şekil 5B). Normal bir solunum gözlenmelidir.</li>
	<li>Kılavuzlu kaval kemiğinin (Bölüm A) açılışında ince uç pipetini (Bölüm A) tutun ve farenin akciğerine küçük bir hava kabarcığım (yaklaşık 0,2 mL) insufflate edin. Farenin göğsünde hafif bir enflasyon uygun entübasyonu gösterir. İnce uç pipetini toz uygulamadan önce çıkarın.</li>
</ol>4. Toz yönetimi
<ol><li>Şırınna bağlı toz yüklü ucu adım 1.5'te açıklandığı gibi tutun. Şırınd ile uç arasındaki hava akışının kesildiğini sağlayın.</li>
	<li>Şırınd pistonu geriye doğru çekerek 0,6 mL havayı geri çekin. NOT: Tozu dağıtmak için kullanılan hava hacmi tozun özelliklerine ve yüklenen toz miktarına bağlıdır. Bu, sonuç bölümünde daha ayrıntılı olarak açıklanmıştır.</li>
	<li>Şırıngam ile toz yüklü uç arasındaki hava akışını bağlamak için üç yönlü stopcock'un vanasını çevirin.</li>
	<li>Toz yüklü ucu farenin nefes borusuna yerleştirilmiş kılavuz kanüle yerleştirin (Şekil 5C). Kılavuz kanül tutun ve tozu aerosol olarak akciğere dağıtmak için şırıngan pistonu tek bir sürekli eylemde zorla itin. NOT: Hayvanın yaralanmasını önlemek için cihazın ileriye doğru hareketi en aza indirilmelidir.</li>
	<li>Ucu çıkarın ve ucun içindeki tozun boşaltılıp boşaltıldığını kontrol edin. Değilse, 4.1 ile 4.4 arasında olan adımı yineleyin. NOT: Toz aşırı dokunma nedeniyle çok sıkı paketlenmişse, düzgün dağıtılamayabilir.</li>
	<li>Yönetim tamamlandıktan sonra, kılavuzlu mayayı nefes borusundan çıkarın.</li>
	<li>Farenin, hava yollarının tıkanmasını önlemek için dilinin yarısı çıkıntılı bir şekilde yatay olarak konumlandırarak iyileşmesine izin verin.</li>
</ol>

<ol>
	<li>Newman, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drug+delivery+to+the+lungs:+challenges+and+opportunities.">Drug delivery to the lungs: challenges and opportunities.</a> Therapeutic Delivery. 8 (8), 647-661 (2017).</li><li>Setter, S. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhaled+dry+powder+insulin+for+the+treatment+of+diabetes+mellitus.">Inhaled dry powder insulin for the treatment of diabetes mellitus.</a> Clinical Therapeutics. 29 (5), 795-813 (2007).</li><li>Muralidharan, P., Hayes, D., Mansour, H. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry+powder+inhalers+in+COPD,+lung+inflammation+and+pulmonary+infections.">Dry powder inhalers in COPD, lung inflammation and pulmonary infections.</a> Expert Opinion on Drug Delivery. 12 (6), 947-962 (2015).</li><li>de Boer, A. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry+powder+inhalation:+past,+present+and+future.">Dry powder inhalation: past, present and future.</a> Expert Opinion on Drug Delivery. 14 (4), 499-512 (2017).</li><li>Das, S., Tucker, I., Stewart, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhaled+dry+powder+formulations+for+treating+tuberculosis.">Inhaled dry powder formulations for treating tuberculosis.</a> Current Drug Delivery. 12 (1), 26-39 (2015).</li><li>Okamoto, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stability+of+chitosan-pDNA+complex+powder+prepared+by+supercritical+carbon+dioxide+process.">Stability of chitosan-pDNA complex powder prepared by supercritical carbon dioxide process.</a> International Journal of Pharmaceutics. 290 (1-2), 73-81 (2005).</li><li>He, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+inhaled+recombinant+human+insulin+dry+powders:+pharmacokinetics,+pharmacodynamics+and+14-day+inhalation.">Evaluation of inhaled recombinant human insulin dry powders: pharmacokinetics, pharmacodynamics and 14-day inhalation.</a> Journal of Pharmacy and Pharmacology. 71 (2), 176-184 (2019).</li><li>Durham, P. G., Young, E. F., Braunstein, M. S., Welch, J. T., Hickey, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+dry+powder+combination+of+pyrazinoic+acid+and+its+n-propyl+ester+for+aerosol+administration+to+animals.">A dry powder combination of pyrazinoic acid and its n-propyl ester for aerosol administration to animals.</a> International Journal of Pharmaceutics. 514 (2), 384-391 (2016).</li><li>Phillips, J. E., Zhang, X., Johnston, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry+powder+and+nebulized+aerosol+inhalation+of+pharmaceuticals+delivered+to+mice+using+a+nose-only+exposure+system.">Dry powder and nebulized aerosol inhalation of pharmaceuticals delivered to mice using a nose-only exposure system.</a> JoVE (Journal of Visualized Experiments). (122), e55454 (2017).</li><li>Nahar, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vitro,+in+vivo+and+ex+vivo+models+for+studying+particle+deposition+and+drug+absorption+of+inhaled+pharmaceuticals).">In vitro, in vivo and ex vivo models for studying particle deposition and drug absorption of inhaled pharmaceuticals).</a> European Journal of Pharmaceutical Sciences. 49 (5), 805-818 (2013).</li><li>Price, D. N., Muttil, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Delivery+of+Therapeutics+to+the+Lung.">Delivery of Therapeutics to the Lung.</a> Methods in Molecular Biology. 1809, 415-429 (2018).</li><li>Chang, R. Y. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Proof-of-Principle+Study+in+a+Murine+Lung+Infection+Model+of+Antipseudomonal+Activity+of+Phage+PEV20+in+a+Dry-Powder+Formulation.">Proof-of-Principle Study in a Murine Lung Infection Model of Antipseudomonal Activity of Phage PEV20 in a Dry-Powder Formulation.</a> Antimicrobial Agents and Chemotherapy. 62 (2), (2018).</li><li>Ito, T., Okuda, T., Takayama, R., Okamoto, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Establishment+of+an+Evaluation+Method+for+Gene+Silencing+by+Serial+Pulmonary+Administration+of+siRNA+and+pDNA+Powders:+Naked+siRNA+Inhalation+Powder+Suppresses+Luciferase+Gene+Expression+in+the+Lung.">Establishment of an Evaluation Method for Gene Silencing by Serial Pulmonary Administration of siRNA and pDNA Powders: Naked siRNA Inhalation Powder Suppresses Luciferase Gene Expression in the Lung.</a> Journal of pharmaceutical sciences. 108 (8), 2661-2667 (2019).</li><li>Patil, J. S., Sarasija, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pulmonary+drug+delivery+strategies:+A+concise,+systematic+review.">Pulmonary drug delivery strategies: A concise, systematic review.</a> Lung India. 29 (1), 44-49 (2012).</li><li>Ihara, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Histological+Quantification+of+Gene+Silencing+by+Intratracheal+Administration+of+Dry+Powdered+Small-Interfering+RNA/Chitosan+Complexes+in+the+Murine+Lung.">Histological Quantification of Gene Silencing by Intratracheal Administration of Dry Powdered Small-Interfering RNA/Chitosan Complexes in the Murine Lung.</a> Pharmaceutical Research. 32 (12), 3877-3885 (2015).</li><li>Qiu, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effective+mRNA+pulmonary+delivery+by+dry+powder+formulation+of+PEGylated+synthetic+KL4+peptide.">Effective mRNA pulmonary delivery by dry powder formulation of PEGylated synthetic KL4 peptide.</a> Journal of Controlled Release. 314, 102-115 (2019).</li><li>Pfeifer, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry+powder+aerosols+of+polyethylenimine+(PEI)-based+gene+vectors+mediate+efficient+gene+delivery+to+the+lung.">Dry powder aerosols of polyethylenimine (PEI)-based gene vectors mediate efficient gene delivery to the lung.</a> Journal of Controlled Release. 154 (1), 69-76 (2011).</li><li>Kim, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Doxorubicin-loaded+highly+porous+large+PLGA+microparticles+as+a+sustained-+release+inhalation+system+for+the+treatment+of+metastatic+lung+cancer.">Doxorubicin-loaded highly porous large PLGA microparticles as a sustained- release inhalation system for the treatment of metastatic lung cancer.</a> Biomaterials. 33 (22), 5574-5583 (2012).</li><li>Tonnis, W. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+aerosol+generator+for+homogenous+distribution+of+powder+over+the+lungs+after+pulmonary+administration+to+small+laboratory+animals.">A novel aerosol generator for homogenous distribution of powder over the lungs after pulmonary administration to small laboratory animals.</a> European Journal of Pharmaceutics and Biopharmaceutics. 88 (3), 1056-1063 (2014).</li><li>Hoppentocht, M., Hoste, C., Hagedoorn, P., Frijlink, H. W., de Boer, A. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vitro+evaluation+of+the+DP-4M+PennCentury+insufflator.">In vitro evaluation of the DP-4M PennCentury insufflator.</a> European Journal of Pharmaceutics and Biopharmaceutics. 88 (1), 153-159 (2014).</li><li>Liao, Q., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Porous+and+highly+dispersible+voriconazole+dry+powders+produced+by+spray+freeze+drying+for+pulmonary+delivery+with+efficient+lung+deposition.">Porous and highly dispersible voriconazole dry powders produced by spray freeze drying for pulmonary delivery with efficient lung deposition.</a> International Journal of Pharmaceutics. 560, 144-154 (2019).</li><li>Ito, T., Okuda, T., Takashima, Y., Okamoto, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Naked+pDNA+Inhalation+Powder+Composed+of+Hyaluronic+Acid+Exhibits+High+Gene+Expression+in+the+Lungs.">Naked pDNA Inhalation Powder Composed of Hyaluronic Acid Exhibits High Gene Expression in the Lungs.</a> Molecular Pharmaceutics. 16 (2), 489-497 (2019).</li><li>Chaurasiya, B., Zhou, M., Tu, J., Sun, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Design+and+validation+of+a+simple+device+for+insufflation+of+dry+powders+in+a+mice+model.">Design and validation of a simple device for insufflation of dry powders in a mice model.</a> European Journal of Pharmaceutical Sciences. 123, 495-501 (2018).</li></ol>

Yazarların açıklayacak çıkar çatışmaları yoktur.

Bu yazıda kuru toz insufflation ve intratrakial entübasyon için özel yapım cihazlar sunulmuştur. Toz yükleme adımında, kuru toz 200 μL jel yükleme pipet ucuna yüklenir. Ucun dar ucunda gevşek toz paketlemeye izin vermek için uca hafifçe dokunmak önemlidir. Bununla birlikte, toz çok sıkı paketlenirse, ucuna sıkışırlar ve düzgün bir şekilde dağılamazlar. Özellikle düşük yoğunluklu ve düşük bağıl nemde toz yüklemesini kolaylaştırmak için tozun ve pipet ucunun statik yüklerinin nöt...

Pulmoner uygulama yolu, hem lokal hem de sistemik eylemler için terapötiklerin sağlanmasında çeşitli faydalar sunmaktadır. Akciğer hastalıklarının tedavisi için, pulmoner doğumla yüksek lokal ilaç konsantrasyonu elde edilebilir, böylece gerekli doz azaltılabilir ve sistemik yan etkilerin insidansı düşürülebilir. Ayrıca, akciğerdeki nispeten düşük enzimamatik aktiviteler erken ilaç metabolizmasını azaltabilir. Akciğerler ayrıca büyük ve iyi perfüzyonlu yüzey alanı, son derece ince epitel hücre tabakası ve pulmoner kılcal damarlardaki yüksek kan hacmi nedeniyle sistemik etki için ilaç emilimi için de etkilidir1.
Solunan kuru toz formülasyonları astım, kronik obstrüktif akciğer hastalığı, diabetes mellitus ve pulmoner aşılama 2,3 ,4gibi çeşitli hastalıkların önlenmesi ve tedavisi için yaygın olarak araştırılmıştır. Katı durumdaki ilaçlar genellikle sıvı formda olduğundan daha kararlıdır ve kuru toz inhalatörleri nebülizörlerden daha taşınabilir ve kullanıcı dostudur5,6. Solunan kuru toz formülasyonlarının geliştirilmesinde, pulmoner uygulamadan sonra preklinik hayvan modellerinde güvenlik, farmakokinetik profil ve terapötik etkinliğin değerlendirilmesi gerekir7. Kuru tozu aktif olarak soluyabilen insanların aksine, kuru tozun küçük hayvanlara pulmoner teslimatı zordur. Hayvanların akciğerlerine kuru toz teslim etmek için verimli bir protokol oluşturmak gerekir.
Fareler, ekonomik oldukları ve iyi üredikleri için araştırma hayvanı modelleri olarak yaygın olarak kullanılmaktadır. Ayrıca kullanımı kolaydır ve birçok hastalık modeli iyi kurulmuştur. Kuru tozu farenin akciğerine uygulamak için iki ana yaklaşım vardır: soluma ve intratrakiyeal uygulama. Soluma için, fare kuru tozun aerosolleştirildiği ve hayvanların sakinleştirilmeden aerosolde nefes aldığı tüm vücut veya sadece burun odasına yerleştirilir8,9. Pahalı ekipman gereklidir ve ilaç dağıtım verimliliği düşüktür. Tüm vücut odası teknik olarak daha az zorlu olsa da, sadece burun maruziyet odası ilaçların vücut yüzeyine maruz kalmasını en aza indirebilir. Ne olursa olsun, akciğerlere teslim edilen dozu hassas bir şekilde kontrol etmek ve belirlemek hala zordur. Kuru toz esas olarak mukozal boşluğun belirgin olduğu nazofarenks bölgesinde biriktirilir10. Ayrıca, odanın içindeki fareler yönetim sürecinde önemli bir stres altındadır, çünkü kısıtlanmış ve yiyecek ve su temininden mahrumdurlar11. Intratraseral uygulama için, genellikle maddenin doğrudan nefes borusuna girmesini ifade eder. Bunu başarmak için iki farklı teknik vardır: trakeotomi ve orotrakeal entübasyon. Birincisi, trakeada bir kesi yapan cerrahi bir prosedür gerektirir, bu da invazivdir ve nadiren toz uygulama için kullanılır. Burada sadece ikinci teknik açıklanmıştır. Soluma yöntemi ile karşılaştırıldığında, intratrakiel uygulama, minimum ilaç kaybı ile yüksek teslimat verimliliği nedeniyle farede pulmoner doğum için daha yaygın kullanılan yöntemdir12,13. Fareye birkaç miligram içinde az miktarda toz teslim etmek basit ve hızlı bir yöntemdir. Fare anatomik ve fizyolojik olarak insanlara farklı olmasına ve entübasyon işlemi sırasında anestezi yapılması gerekmesine rağmen, intratrakimyasal uygulama üst solunum yollarını atlar ve pulmoner emilim, biyoyararlanım ve terapötik etkiler gibi kuru toz formülasyonunun biyolojik aktivitelerini değerlendirmek için daha etkili bir yol sunar14,15.
Kuru tozu intratrakisel olarak uygulamak için, farenin entübe edilmesi gerekir, bu da zor olabilir. Bu yazıda, özel yapım kuru toz insufflator ve entübasyon cihazının imalatı açıklanmıştır. Farenin akciğerinde kuru tozun entübasyon ve insufflation işlemleri gösterilmiştir.

<table>
	<tbody>
		<tr>
			<td>BALB/c mouse</td>
			<td></td>
			<td></td>
			<td>Female; 7-9 weeks old; Body weight 20-25 g</td>
		</tr>
		<tr>
			<td>CleanCap Firefly Luciferase mRNA</td>
			<td>TriLink Biotechnology</td>
			<td>L-7602</td>
			<td></td>
		</tr>
		<tr>
			<td>Dry Powder Insufflator</td>
			<td>PennCentury</td>
			<td>Model DP-4M</td>
			<td></td>
		</tr>
		<tr>
			<td>Ketamine 10%</td>
			<td>Alfasan International B.V.</td>
			<td>NA</td>
			<td></td>
		</tr>
		<tr>
			<td>Light emitting diode (LED) torch</td>
			<td>Unilite Internation</td>
			<td>PS-K1</td>
			<td></td>
		</tr>
		<tr>
			<td>Mannitol (Pearlitol 160C)</td>
			<td>Roquette</td>
			<td>450001</td>
			<td></td>
		</tr>
		<tr>
			<td>Non-filter round gel loading pipette tip (200 &#181;L)</td>
			<td>Labcon</td>
			<td>1034-800-000</td>
			<td></td>
		</tr>
		<tr>
			<td>Nylon floss</td>
			<td>Reach</td>
			<td>30017050</td>
			<td></td>
		</tr>
		<tr>
			<td>One milliliter syringe without needle</td>
			<td>Terumo</td>
			<td>SS-01T</td>
			<td></td>
		</tr>
		<tr>
			<td>Optical fibre</td>
			<td>Fibre Data</td>
			<td>OMPF1000</td>
			<td></td>
		</tr>
		<tr>
			<td>PEG12KL4 peptide</td>
			<td>EZ Biolab</td>
			<td></td>
			<td>(PEG12)-KLLLLKLLLLKLLLLKLLLLK-NH2</td>
		</tr>
		<tr>
			<td>Plastic Pasteur fine tip pipette</td>
			<td>Alpha Labotatories</td>
			<td>LW4061</td>
			<td></td>
		</tr>
		<tr>
			<td>Three-way stopcock</td>
			<td>Braun</td>
			<td>D201</td>
			<td></td>
		</tr>
		<tr>
			<td>Xylazine 2%</td>
			<td>Alfasan International B.V.</td>
			<td>NA</td>
			<td></td>
		</tr>
		<tr>
			<td>Zerostat 3 anti-static gun</td>
			<td>MILTY</td>
			<td>5036694022153</td>
			<td></td>
		</tr>
	</tbody>
</table>

intratracheal administration of dry powder formulation in mice

Solunabilir kuru toz formülasyonlarının geliştirilmesinde, biyolojik faaliyetlerini preklinik hayvan modellerinde değerlendirmek esastır. Bu makale, farelerde kuru toz formülasyonunun intratraskial teslimatının noninvaziv bir yöntemini tanıtmaktadır. Üç yönlü bir stopcock aracılığıyla 1 mL şırındıya bağlı 200 μL jel yükleme pipet ucundan oluşan kuru toz yükleme cihazı sunulur. Pipet ucuna az miktarda kuru toz (1-2 mg) yüklenir ve şırınnada 0,6 mL hava ile dağılır. Pipet uçları tek kullanımlık ve ucuz olduğundan, farklı kuru toz formülasyonları önceden farklı uçlara yüklenebilir. Çeşitli formülasyonlar, cihaz temizliği ve doz doldurma olmadan aynı hayvan deneyinde değerlendirilebilir, böylece zamandan tasarruf edilir ve artık tozdan çapraz bulaşma riski ortadan kalkar. Toz dağılımının kapsamı pipet ucunda kalan toz miktarına göre incelenebilir. Farede özel yapım ışık kaynağı ve yol gösterici bir canül içeren bir entübasyon protokolü dahildir. Uygun entübasyon, kuru toz formülasyonunun farenin derin akciğer bölgesine intratrakial olarak teslimini etkileyen önemli faktörlerden biridir.

Bir hayvanın akciğerine toz aerosol sağlamak için kuru bir toz oyucu kullanıldığında, kullanılan hava hacmi, toz dağılımı verimliliğinin yanı sıra güvenliği de etkilediği için kritik öneme sahiptir. Yöntemi optimize etmek için, kuru tozu dağıtmak için farklı hava hacimleri (0,3 mL, 0,6 mL ve 1,0 mL) kullanıldı (1 mg sprey kurutulmuş mannitol) ve farelerin ağırlığı uygulamadan sonra 48 saat boyunca izlendi(Şekil 6). 0.3 mL ve 0.6 mL hava kullanımı, farele...

Watch this Scientific Journal Video about Intratracheal Administration of Dry Powder Formulation in Mice at JoVE.com

Intratracheal Administration of Dry Powder Formulation in Mice

Soluma için kuru toz formülasyonları solunum yolu hastalıklarının tedavisinde büyük potansiyele sahiptir. İnsan çalışmalarına girmeden önce, preklinik çalışmalarda kuru toz formülasyonunun etkinliğini değerlendirmek gerekir. Farelerde intratrakiel yoldan kuru tozun yönetiminin basit ve invaziv bir yöntemi sunulmuştur.

Farelerde Kuru Toz Formülasyonunun Intratrakial Yönetimi

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

intratracheal-administration-of-dry-powder-formulation-in-mice

Research

JoVE Journal

Medicine

9.7K Görüntüleme.  The University of Hong Kong. Soluma için kuru toz formülasyonları solunum yolu hastalıklarının tedavisinde büyük potansiyele sahiptir. İnsan çalışmalarına girmeden önce, preklinik çalışmalarda kuru toz formülasyonunun etkinliğini değerlendirmek gerekir. Farelerde intratrakiel yoldan kuru tozun yönetiminin basit ve invaziv bir yöntemi sunulmuştur.

Video: Intratracheal Administration of Dry Powder Formulation in Mice

A Novel Surgical Approach for Intratracheal Administration of Bioactive Agents in a Fetal Mouse Model

Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide the basis for new therapeutic strategies for a variety of genetic and acquired diseases. Apart from congenital or inherited abnormalities with the requirement for long-term expression of the delivered gene, several non-inherited perinatal conditions, where short-term gene expression or pharmacological intervention is sufficient to achieve therapeutic effects, are considered as potential future indications for this kind of approach. Candidate diseases for the application of short-term prenatal therapy could be the transient neonatal deficiency of surfactant protein B causing neonatal respiratory distress syndrome1,2 or hyperoxic injuries of the neonatal lung3. Candidate diseases for permanent therapeutic correction are Cystic Fibrosis (CF)4, genetic variants of surfactant deficiencies5 and &alpha;1-antitrypsin deficiency6.
Generally, an important advantage of prenatal gene therapy is the ability to start therapeutic intervention early in development, at or even prior to clinical manifestations in the patient, thus preventing irreparable damage to the individual. In addition, fetal organs have an increased cell proliferation rate as compared to adult organs, which could allow a more efficient gene or stem cell transfer into the fetus. Furthermore, in utero gene delivery is performed when the individual's immune system is not completely mature. Therefore, transplantation of heterologous cells or supplementation of a non-functional or absent protein with a correct version should not cause immune sensitization to the cell, vector or transgene product, which has recently been proven to be the case with both cellular and genetic therapies7.
In the present study, we investigated the potential to directly target the fetal trachea in a mouse model. This procedure is in use in larger animal models such as rabbits and sheep8, and even in a clinical setting9, but has to date not been performed before in a mouse model. When studying the potential of fetal gene therapy for genetic diseases such as CF, the mouse model is very useful as a first proof-of-concept because of the wide availability of different transgenic mouse strains, the well documented embryogenesis and fetal development, less stringent ethical regulations, short gestation and the large litter size.
Different access routes have been described to target the fetal rodent lung, including intra-amniotic injection10-12, (ultrasound-guided) intrapulmonary injection13,14 and intravenous administration into the yolk sac vessels15,16 or umbilical vein17. Our novel surgical procedure enables researchers to inject the agent of choice directly into the fetal mouse trachea which allows for a more efficient delivery to the airways than existing techniques18.

We developed a novel surgical approach for intratracheal administration of bioactive agents into the mouse fetus. The delivery route is more efficient in targeting the fetal mouse lungs than the commonly used intra-amniotic injection. This procedure has to date not been described in a mouse model.

Bir Fetal Fare Modelinde Biyoaktif Ajan intratrakeal Yönetimi İçin Yeni Bir Cerrahi Yaklaşım

Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide the basis for new therapeutic strategies for a variety of genetic and ...

Tıp

Intranasal Administration of CNS Therapeutics to Awake Mice

Intranasal administration is a method of delivering therapeutic agents to the central nervous system (CNS). It is non-invasive and allows large molecules that do not cross the blood-brain barrier access to the CNS. Drugs are directly targeted to the CNS with intranasal delivery, reducing systemic exposure and thus unwanted systemic side effects1. Delivery from the nose to the CNS occurs within minutes along both the olfactory and trigeminal neural pathways via an extracellular route and does not require drug to bind to any receptor or axonal transport2. Intranasal delivery is a widely publicized method and is currently being used in human clinical trials3.
Intranasal delivery of drugs in animal models allows for initial evaluation of pharmacokinetic distribution and efficacy. With mice, it is possible to administer drugs to awake (non-anesthetized) animals on a regular basis using a specialized intranasal grip. Awake delivery is beneficial because it allows for long-term chronic dosing without anesthesia, it takes less time than with anesthesia, and can be learned and done by many people so that teams of technicians can dose large numbers of mice in short periods. Efficacy of therapeutics administered intranasally in this way to mice has been demonstrated in a number of studies including insulin in diabetic mouse models 4-6 and deferoxamine in Alzheimer's mouse models. 7,8
The intranasal grip for mice can be learned, but is not easy and requires practice, skill, and a precise grip to effectively deliver drug to the brain and avoid drainage to the lung and stomach. Mice are restrained by hand using a modified scruff in the non-dominant hand with the neck held parallel to the floor, while drug is delivered with a pipettor using the dominant hand. It usually takes 3-4 weeks of acclimating to handling before mice can be held with this grip without a stress response. We have prepared this JoVE video to make this intranasal delivery technique more accessible.

A method to intranasally administer drugs to awake mice for the purpose of targeting the brain is described. This method allows for repeat dosing over long periods using intranasal administration of drug without anesthesia, and nose-to-brain delivery with minimal systemic exposure.

Uyanık Fare CNS Therapeutics İntranazal İdaresi

Intranasal administration is a method of delivering  therapeutic agents to the central nervous system (CNS). It is  non-invasive and allows large ...

Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice Using a Nose-only Exposure System

Obstructive respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD) are currently treated by inhaled anti-inflammatory and bronchodilator drugs. Despite the availability of multiple treatments, both diseases are growing public health concerns. The majority of asthma patients are well controlled on current inhaled therapies but a substantial number of patients with severe asthma are not. Asthma affects an estimated 300 million people worldwide and approximately 20 percent have a severe form of the disease. In contrast to asthma, there are few effective therapies for COPD. An estimated 10% of the population has COPD and the trend in death rates is increasing for COPD while decreasing for other major diseases. Although developing drugs for inhaled delivery is challenging, the nose-only inhalation unit enables direct delivery of novel drugs to the lung of rodents for pre-clinical efficacy and safety/toxicology studies. Inhaled drug delivery has multiple advantages for respiratory diseases, where high concentration in the lung improves efficacy and minimizes systemic side effects. Inhaled corticosteroids and bronchodilators benefit from these advantages and inhaled delivery may also hold potential for future biologic therapies. The inhalation unit described herein can generate, sample for characterization, and uniformly deposit a drug aerosol in the lungs of rodents. This enables the pre-clinical determination of the efficacy and safety of drug doses deposited in the lungs of rodents, key data required before initiating clinical development.

The inhalation unit described herein can generate, sample for characterization, and uniformly deposit a drug aerosol in the lungs of rodents. This enables the pre-clinical determination of the efficacy and safety of drug doses deposited in the lungs; key data enabling clinical inhaled drug development.

Kuru Toz ve Eczacılık Nebulize Aerosol Soluma bir Burun sadece Pozlama Sistemi Kullanarak Fare teslim

Obstructive respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD) are currently treated by inhaled anti-inflammatory and ...

A Pleural Effusion Model in Rats by Intratracheal Instillation of Polyacrylate/Nanosilica

Pleural effusion is a prevalent clinical finding of many pulmonary diseases. Having a useful animal pleural effusion model is very important to study these pulmonary diseases. Previous pleural effusion models paid more attention to biological factors rather than nanoparticles in the environment. Here, we introduce a model to make pleural effusion in rats by intratracheal instillation of polyacrylate/nanosilica, and a method of nanoparticle isolation in the pleural effusion. By intratracheal instillation of polyacrylate/nanosilica with concentrations of 3.125, 6.25 and 12.5 mg/kg&#8729;mL, the pleural effusion in rats presented on day 3, peaked at days 7-10 in 6.25 and 12.5 mg/kg&#8729;mL groups, then slowly decreased and disappeared on day 14. When the concentration of polyacrylate/nanosilica increased, the pleural effusion is produced more and faster. This pleural fluid was detected by ultrasound examination or CT chest scanning and confirmed by dissection of rats. Silica nanoparticles were observed in the rats' pleural effusion by transmission electron microscope. These results showed that the exposure to polyacrylate/nanosilica leads to the induction of pleural effusion, which was consistent with our previous report in humans. Additionally, this model is beneficial for the further study of nanotoxicology and the pleural effusion diseases.

Here, we present a protocol to construct a pleural effusion model in rats by intratracheal instillation of polyacrylate/nanosilica.

Plevral efüzyon manken poliakrilat/Nanosilica boğaza korumak tarafından Sıçanlarda

Pleural effusion is a prevalent clinical finding of many pulmonary diseases. Having a useful animal pleural effusion model is very important to study ...

Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation

Airway administration of lipopolysaccharide (LPS) is a common way to study pulmonary inflammation and acute lung injury (ALI) in small animal models. Various approaches have been described, such as the inhalation of aerosolized LPS as well as nasal or intratracheal instillation. The presented protocol describes a detailed step-by-step procedure to induce ALI in mice by direct intratracheal LPS instillation and perform FACS analysis of blood samples, bronchoalveolar lavage (BAL) fluid, and lung tissue. After intraperitoneal sedation, the trachea is exposed and LPS is administered via a 22 G venous catheter. A robust and reproducible inflammatory reaction with leukocyte invasion, upregulation of proinflammatory cytokines, and disruption of the alveolo-capillary barrier is induced within hours to days, depending on the LPS dosage used. Collection of blood samples, BAL fluid, and lung harvesting, as well as the processing for FACS analysis, are described in detail in the protocol. Although the use of the sterile LPS is not suitable to study pharmacologic interventions in infectious diseases, the described approach offers minimal invasiveness, simple handling, and good reproducibility to answer mechanistic immunological questions. Furthermore, dose titration as well as the use of alternative LPS preparations or mouse strains allow modulation of the clinical effects, which can exhibit different degrees of ALI severity or early vs. late onset of disease symptoms.

Presented here is a step-by-step procedure to induce acute lung injury in mice by direct intratracheal lipopolysaccharide instillation and to perform FACS analysis of blood samples, bronchoalveolar lavage fluid, and lung tissue. Minimal invasiveness, simple handling, good reproducibility, and titration of disease severity are advantages of this approach.

Doğrudan Intratracheal Lipopolysaccharide Instilasyon ile farelerde akut akciğer hasarının İndükleme

Airway administration of lipopolysaccharide (LPS) is a common way to study pulmonary inflammation and acute lung injury (ALI) in small animal models. ...

Establishment of a Severe Dry Eye Model Using Complete Dacryoadenectomy in Rabbits

Dry eye disease (DED) is a complex disease with multiple etiologies and variable symptoms, having ocular surface inflammation as its key pathophysiologic step. Despite advances in our understanding of DED, significant knowledge gaps remain. Advances are limited in part due to the lack of informative animal models. The authors recently reported on a method of DED induced by injecting all orbital lacrimal gland (LG) tissues with the lectin concanavalin A. Here, we report a novel model of aqueous-deficient DED based on the surgical resection of all orbital LG (dacryoadenectomy) tissues. Both methods use rabbits because of their similarity to human eyes in terms of the size and structure of the ocular surface. One week after removal of the nictitating membrane, the orbital superior LG was surgically removed under anesthesia, followed by removal of the palpebral superior LG, and finally removal of the inferior LG. Dacryoadenectomy induced severe DED, evidenced by a marked reduction in the tear break up time test and the Schirmer&#39;s tear test, and significantly increased tear osmolarity and rose bengal staining. Dacryoadenectomy-induced DED lasted at least eight weeks. There were no complications and animals tolerated the procedure well. The technique can be mastered relatively easily by those with adequate surgical experience and appreciation of the relevant rabbit anatomy. Since this model recapitulates the features of human aqueous-deficient DED, it is suitable for studies of ocular surface homeostasis, DED, and candidate therapeutics.

A novel approach is presented to induce chronic dry eye disease in rabbits by surgically removing all orbital lacrimal glands. This method, distinct from those previously reported, produces a stable, reproducible model of aqueous deficient dry eye well suited to study tear physiology and pathophysiology and ocular therapeutics.

Tavşanlarda Komple Dakriyoadenektomi Kullanarak Şiddetli Kuru Göz Modelinin Oluşturulması

Dry eye disease (DED) is a complex disease with multiple etiologies and variable symptoms, having ocular surface inflammation as its key pathophysiologic ...

Intratracheal Instillation of Stem Cells in Term Neonatal Rats

Prolonged exposure to high concentrations of oxygen leads to inflammation and acute lung injury, which is similar to human bronchopulmonary dysplasia (BPD). In premature infants, BPD is a major complication despite early use of surfactant therapy, optimal ventilation strategies, and noninvasive positive pressure ventilation. Because pulmonary inflammation plays a crucial role in the pathogenesis of BPD, corticosteroid use is one potential treatment to prevent it. Nevertheless, systemic corticosteroid treatment is not usually recommended for preterm infants due to long-term adverse effects. Preclinical studies and human phase I clinical trials demonstrated that use of mesenchymal stromal cells (MSCs) in hyperoxia-induced lung injuries and in preterm infants is safe and feasible. Intratracheal and intravenous MSC transplantation has been shown to protect against neonatal hyperoxic lung injury. Therefore, intratracheal administration of stem cells and combined surfactant and glucocorticoid treatment has emerged as a new strategy to treat newborns with respiratory disorders. The developmental stage of rat lungs at birth is equivalent to that in human lungs at 26&#8722;28 week of gestation. Hence, newborn rats are appropriate for studying intratracheal administration to preterm infants with respiratory distress to evaluate its efficacy. This intratracheal instillation technique is a clinically viable option for delivery of stem cells and drugs into the lungs.

Described is a protocol for performing intratracheal transplantation of mesenchymal stromal cells (MSCs) through intratracheal injection in term neonatal rats. This technique is a clinically viable option for delivery of stem cells and drugs into neonatal rat lungs to evaluate their efficacy.

Dönem Yenidoğan Sıçanlarda Kök Hücrelerin İntratrakeal Aşılanması

Prolonged exposure to high concentrations of oxygen leads to inflammation and acute lung injury, which is similar to human bronchopulmonary dysplasia ...

A Minimally Invasive Method for Intratracheal Instillation of Drugs in Neonatal Rodents to Treat Lung Disease

Treatment of neonatal rodent with drugs instilled directly into the trachea could serve as a valuable tool to study the impact of a locally administered drug. This has direct translational impact because surfactant and drugs are administered locally into the lungs. Though the literature has many publications describing minimally invasive transoral intubation of adult mice and rats in therapeutic experiments, this approach in neonatal rat pups is lacking. The small size of orotracheal region/pharynx in the pups makes visualization of laryngeal lumen (vocal cords) difficult, contributing to the variable success rate of intratracheal drug delivery. We hereby demonstrate effective oral intubation of neonatal rat pup - a technique that is non-traumatic and minimally-invasive, so that it can be used for serial administration of drugs. We used an operating otoscope with an illumination system and a magnifying lens to visualize the tracheal opening of the rat neonates. The drug is then instilled using a 1 mL syringe connected to a pipette tip. The accuracy of the delivery method was demonstrated using Evans blue dye administration. This method is easy to get trained in and could serve as an effective way to instill drugs into trachea. This method could also be used for administration of inoculum or agents to simulate disease conditions in animals and, also, for cell-based treatment strategies for various lung diseases.

This technique of instilling drugs directly into the trachea of neonatal rodents is important in studying the impact of locally administered drugs or biologicals on neonatal lung diseases. Additionally, this method can also be used for inducing lung injury in animal models.

Yenidoğan Kemirgenlerinde Akciğer Hastalığını Tedavi Etmek İçin İlaçların İntratrakeal İnstilasyonu İçin Minimal İnvaziv Bir Yöntem

Treatment of neonatal rodent with drugs instilled directly into the trachea could serve as a valuable tool to study the impact of a locally administered ...

Customizable Disposable Dosators to Deliver Dry Powder Aerosol Drugs to Mice

Disposable Dosators Intended for Dry Powder Delivery to Mice

Dry powder inhalers offer numerous advantages for delivering drugs to the lungs, including stable solid-state drug formulations, device portability, bolus metering and dosing, and a propellant-free dispersal mechanism. To develop pharmaceutical dry powder aerosol products, robust in vivo testing is essential. Typically, initial studies involve using a murine model for preliminary evaluation before conducting formal studies in larger animal species. However, a significant limitation in this approach is the lack of suitable device technology to accurately and reproducibly deliver dry powders to small animals, hindering such models&#39; utility. To address these challenges, disposable syringe dosators were developed specifically for intrapulmonary delivery of dry powders in doses appropriate for mice. These dosators load and deliver a predetermined amount of powder obtained from a uniform bulk density powder bed. This discrete control is achieved by inserting a blunt needle to a fixed depth (tamping) into the powder bed, removing a fixed quantity each time. Notably, this dosing pattern has proven effective for a range of spray-dried powders. In experiments involving four different model spray-dried powders, the dosators demonstrated the ability to achieve doses within the range of 30 to 1100 &#181;g. The achieved dose was influenced by factors such as the number of tamps, the size of the dosator needle, and the specific formulation used. One of the key benefits of these dosators is their ease of manufacturing, making them accessible and cost-effective for delivering dry powders to mice during initial proof-of-concept studies. The disposable nature of the dosators facilitates use in animal procedure rooms, where cleaning and refilling reusable systems and weighing materials is inconvenient. Thus, developing disposable syringe dosators has addressed a significant hurdle in murine dry powder delivery for proof-of-concept studies, enabling researchers to conduct more accurate and reproducible preliminary studies in small animal models for pulmonary drug delivery.

Author Spotlight: Developing a Disposable Dosator for Preclinical Testing of Dry Powder Inhalers in Small Animal Models 

Pharmaceutical dry powder development necessitates reliable in vivo testing, often using a murine model. Device technology for accurately and reproducibly delivering dry powder aerosols to mice is restricted. This study presents disposable dosators for pulmonary drug delivery at mouse-relevant doses, aiding initial proof-of-concept research.

Farelere kuru toz verilmesi için tasarlanmış tek kullanımlık dozlayıcılar

Dry powder inhalers offer numerous advantages for delivering drugs to the lungs, including stable solid-state drug formulations, device portability, bolus ...