Bu çalışma Farris Aile İnovasyon Ödülü ve MK NIH 1R01NR015674-01 tarafından desteklenmiştir. Yazarlar elektro-manyetik jeneratör sistemi yanı sıra, onun teknik danışmanlık sağlamak için Josep Nayfach (Qteris, Inc) teşekkür ederim. Yazarlar ayrıca onun teknik asistanlar için Huan Yan (LCI ve Kimya Fizik Disiplinlerarası Programı, Kent State Üniversitesi) teşekkür ederim.

Not: Manyetik alan-duyarlı jelatin mikrojellerinin imal genel proses Şekil 1A&#39;da gösterilmiştir. 1. hazırlanması Çözümler ve süspansiyonlar <ol><li> fosfat tamponlu tuzlu su ve 2 ml genipin 20 mg eriterek çapraz bağlayıcı genipin çözeltisi (w / v% 1) hazırlanması (1 x PBS, pH 7.4). Vortex 2 saat süreyle 50 o C su banyosunda çözüm ve yeri tamamen çözümü çözmek için. </li><li> 100 konsantrasyonda olduğu 200 ml PBS içinde (L64 olarak adlandırılır ağırlık M = 2900 Da), poli (etilen glikol), 20 mg -poli (propilen glikol) -poli (etilen glikol) eriterek bir yüzey aktif madde çözeltisi hazırlayın ppm. </li><li> PBS 0.43 ml jelatin 64.5 mg eritilmesi ile% 15 (a / h) jelatin çözeltisi hazırlayın. Çözümü akışkan hale bir sol faz, ulaşıncaya kadar vorteks çözüm ve 37 o C su banyosunda üzerine yerleştirin. th sağlamak için 3 kez - Sonra, jelatin çözeltisi 2 vorteksörnek E homojenliği. </li><li> P (NIPAM- CO -AAm) Model ilaç / MNPS çözeltisi (BSA) hazırlanması: <ol><li> PBS 0.43 ml hidrofilik MNPS 10.75 mg dağılması ve daha sonra% 3 konsantrasyonda olmak için MNP süspansiyon içinde p 12.9 mg (NIPAM- -AAm Co) çözülür (a / h). P artan konsantrasyonu (NIPAM- -AAm Co) mikrojellerin artırılmış yeniden şişebilme davranış elde etmek için kullanılabilir. </li><li> Texas Kırmızı bağlı sığır serum albümini kullanarak (TR-BSA; M ~ 66 kDa W) Model ilaç olarak. P karışımı (NIPAM- -AAm ko) / MNPS TR-BSA, 0.5 mg çözülür. </li></ol></li><li> Daha sonra P (NIPAM- CO -AAm) karışımı / jelatin çözeltisi içine MNPS (0.43 mi) (0.43 mi) ilave edilerek jelatin / p (NIPAM- CO -AAm) / MNPS / BSA çözeltisi (0.86 mi) karışımları hazırlamak iyice homojen bir karışım yapmak için onları girdap. Bu nedenle, polimerler ve MNP konsantrasyonlar nihai karışım başlangıç ​​konsantrasyonları yarısı olmuştur. </li></ol><ol><li> Temiz ve steril behere silikon yağı [polidimetilsiloksan (viskozite 350 cSt)] 15 ml dökün. </li><li> Hemen silikon yağı içinde jelatin / p (NIPAM- CO -AAm) / MNPS / BSA çözeltisi (0.86 mi) önceden hazırlanmış sulu bir karışımını ekleyin ve 900, bir manyetik karıştırma çubuğu ile karıştırıldı yağ fazında sulu bir karışımı emülsiyon haline 30 dakika boyunca 30 o C&#39;de rpm. </li></ol> Sulu çözelti 3. jelleşme ve mikro-damlacıklarının Transferi <ol><li> 50 ml&#39;lik bir tüp içine kaptan emülsiyonun (~ 16 mi) aktarın. </li><li> yağ içinde mikro damlacıkların katılaşma işlemi için 4 ° C&#39;de 10 dakika süre ile boru soğutun. </li><li> 50 ml kadar (4 o C&#39;de) hazırlanan L64 çözeltisi ile tüp doldurun ve şiddetle tüp sallayın. L64 yüzey aktif maddelerin bir kısmı mikrojelleri içinde olacaktır mümkün olabilir. </li><li> 4 O ° C&#39;de 2300 x g&#39;de 20 dakika boyunca santrifüj tüpü </li><li> Regularly tüp tarafında jel parçacıklarının pelet olup olmadığını kontrol edin. parçacıklar görülmeyen durumlarda, aynı hız ve sıcaklıkta 20 dakika daha santrifüj. dikkatli bir şekilde borunun iç duvarı üzerinde oluşturulmuş pelet bozmadan süpernatan devam edin. </li><li> Adımlarını tekrarlayın (3.5) ile (3.3) bir kez daha. Her zaman, mikrojel süspansiyon içinde bir yağ damlacıklarının oluşumunu önlemek için yeni bir tüpe örnek aktarmak. Bu aşamadan sonra, yüzey aktif maddeler ya da yağ damlacıkları Örnek süspansiyon içinde mevcut değildir emin olun. Bununla birlikte, tekrar ayrıştırma adımları başlangıç ​​malzemeleri kaybına neden olabilir. </li></ol> Mikrojellerin 4. kovalent çapraz bağlanması <ol><li> Jel parçacıklarının pelet genipin çözeltisi (Bölüm 1 &#39;de hazırlandı) 2 ml ilave edilir ve çözelti girdaplanarak iyice karıştırın. </li><li> Hızlı bir DES sırasında kovalent çapraz bağlama reaksiyonu başlatmak için 23 o C&#39;de su banyosu içinde süspansiyon tüp transferi(. Örneğin, 5-120 dakika) IRED çapraz bağlantı süresi. </li><li> Çapraz bağlama sonrasında hemen genipin çözeltisi atma PBS içinde yeniden süspansiyon haline getirilmesini mikrojellerinin ve 2300 x g&#39;de (4 ° C) 20 dakika boyunca tüp santrifüjle aşırı bir çapraz bağlayıcılar çıkarın. Gerekirse, dikkatli ayrı bir pipet ile pelet kurdu molası. genipin hala çözelti içinde kalan, bu yıkama aşaması 3 kere tekrar edilebilir. </li><li> Süpernatant atılır ve istenen yoğunlukta PBS içinde tekrar süspansiyon mikrojellerinin (örn., 5 x 10 6 mikrojeller / ml), bir hemasitometre ile sayılmasıyla. </li><li> Mikroskobik gözlemler için bir slayt cam ve bir kapak kayma arasındaki boşlukta mikrojel süspansiyon yük ve epoksi reçine ile kapak kayma sınırını mühür. </li></ol> İlaç Release Tetikleme için Alternatif Manyetik Alan 5. Uygulama <ol><li> sulu ortam içinde mikrojelleri istenen konsantrasyonu ile TüpManyetik bobinler odası. Gerekirse, AMF uygulama sırasında ortamın sıcaklık değişimini izlemek için bir tüp içine, bir fiber optik sıcaklık probu yerleştirin. </li><li> Tanımlanmış bir alan şiddeti (&gt; 5 kA / m) ve belirli bir süre için yüksek frekanslı (&gt; 100 kHz) AMF uygulayın. AMF uygulanmasının ardından santrifüj 2.273 x g&#39;de (4 ° C) ve spektrofotometri ile çevredeki ortama mikrojelin serbest TR-BSA miktarını belirlemek için süpernatan toplamak 20 dakika boyunca örnek tüpü. Teksas Kırmızısı için uyarma ve emisyon dalga boyları sırasıyla 584 nm ve 612 nm dir. </li></ol>

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The authors have nothing to disclose.

Burada anlatılan teknoloji manyeto-termal tetiklenen ilaç salınımı için nanoparçacık-mikrojel melezleri kullanımına ilişkin kavramının bir kanıtı göstermektedir. Bu durum, fiziksel genipin ile çapraz bağlanmış bir mikro üç boyutlu jelatin ağında MNPS ve p (NIPAM- CO -AAm) zinciri tutulmasıyla da elde edilmiştir. Manyetik alan-duyarlı bir platform da model bir ilaç, BSA serbest tetiklenen uzaktan tatbik AMF, yanıt olarak mikro jelin içindeki ısı üretmek için yeterli olmuştur. <...

Uyaranlara yanıt endojen veya eksojen uyaranlara birine yanıt olarak bir sıkı kontrollü ilaç verme sağlayacak ilaç verme sistemleri (örn., Sıcaklık ya da pH) yoğun ilaç iletimi için, akıllı yazılım cihazların yeni türleri incelenmiştir. Mikro hidrojeller yaygın da kontrol edilebilir ve sürdürülebilir bir ilaç salınım profillerini ve ayarlanabilir mekanik ve kimyasal özellikleri 1-3 kazandırmalarıdır bir ilaç verme platformu olarak kullanılmıştır. Özellikle, kolloidal mikrojeller nedeniyle dış uyaranlara ve minimal invaziv bir şekilde 4 yerel dokuya uygun Püskürtülebilirlik onların hızlı yanıt için ilaç dağıtımı için bir araç olarak birçok avantaj sergilemektedir. Poli (N-izopropil akrilamid) (pNIPAM) veya bunun kopolimerleri yaygın jelatin, çitosan, alginat asit ya da hyaluronic asit de dahil olmak üzere biyolojik olarak parçalanabilir / biyo-uyumlu polimerler ile pNIPAM aşılanmasıyla termo-duyarlı mikrojellerinin sentezlenmesi benimsenmiştir 5,6, Burada alt kritik çözelti sıcaklığı (LCST&#39;nin) de pNIPAM bir faz geçiş karakteristiği ilaç salımının 7&#39;nin bir tetikleyici olarak kullanılabilir. Son zamanlarda poli eklenerek biyolojik olarak parçalanabilen, jelatin esaslı termo-duyarlı mikro jelin bir imalat göstermiştir (N-isopropylacrylamide- CO -akrilamit) [p (NIPAM- CO -AAm)], üç boyutlu jelatin ağları 8 içinde küçük bir bileşen olarak zincirler. Jelatin / s (NIPAM- CO -AAm) mikrojel pozitif büyükbaş hayvan serum albümini (BSA) serbest bırakılması için, ilişkili sıcaklık artışı, bir ayarlanabilir büzülme sergilemiştir. Son birkaç yıl içinde, bir on-demand moda 9,10 ilacın salımını tetikleyebilir bir manyetik duyarlı ilaç dağıtım platformu geliştirmek için çabalar artmaktadır. manyetik yanıt ilaç verme platformun sentezi için temel prensip süperparamanyetik nanopartiküllerin özelliği (kullanırbir sıcaklığa duyarlı madde salgılar manyetik alan (AMF), yüksek frekanslı dalgalı aldığınızda MNPS) ısı üretmek için. Bu, bu sistem dokusu içine derin hedef olabilir gelecekteki klinik uygulamalar için umut vaat non-invaziv ve uzaktan kontrollü ilaç salımını sağlayan ve hipertermi tedavisi ve manyetik rezonans görüntüleme sistemiyle 10-12 ile kombine edilebilir. Bu tür platformlar aşağıdakileri içerir: (1) MNPS / pNIPAM hibrid mikrojel tanecikleri 13-15 ve (2) makroskopik hidrojel iskeleleri immobilize da kapsayan MNPS 16-18. pNIPAM tabanlı mikrojel platformları manyetik-termik uyaranlara ince ayarlanabilir hacimli faz geçiş tepki gösterdi. Bununla birlikte, potansiyel olarak in vivo uygulamaları sınırlayabilir hücre 19 için sitotoksik olabilir imalat ve içeriği yüksek olan pNIPAM polimerlerin kullanımında karmaşık ve sofistike teknikler de kullanabilir. makroskopik iskeleleri göreli sergileyenly yavaş dış uyaranlara tepki ve kolloidal mikrojelleri kıyasla invazif cerrahi nakli gerektirir. Su-içinde-yağ emülsiyonlaştırıcı milimetre altı ya mikrometre büyüklüğünde jeli 20 partiküllerinin üretilmesi için standart yöntem olmuştur. emülsiyonun su-yağ arayüz olarak, mikrojel partikül bağlı mekanik kesme kuvveti altında su damlasının yüzey enerjisinin azaltılması için küresel bir şekil oluşturur. Bu yöntem, basit bir üretim prosedürü sulu küresel jel damlacıklarının büyük bir miktarda üretimine olanak sağlayan ve başarılı bir şekilde ilaç verme uygulamaları 21-23 jelatin bazlı mikrojellerinin imal edilmesi için kabul edilmiştir. Burada, su-içinde-yağ emülsiyonlaştırıcı yöntemi ile ilaç verme uygulaması için magnetothermally duyarlı jelatin esaslı mikrojellerinin sentezlemek için, basit bir yöntem sunulmaktadır. Bu fiziksel içeren demir oksit MNPS ve p (NIPAM- eş tarafından sağlandı -AAm) kovalent bir manyetik alan (AMF) uygulama sistemi, yüksek frekanslı dalgalı ile bağlantılı olarak, doğal olarak türetilen çapraz bağlayıcı genipin ile çapraz bir küresel mikro jelatin ağı içinde küçük bir bileşen olarak zincirler.

<table border="0" cellpadding="0" cellspacing="0" width="706">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Gelatin</td>
			<td style="width:204px;">Sigma-Aldrich, MO, USA</td>
			<td style="width:119px;">G2500</td>
			<td style="width:167px;">Gelatin type A, porcine skin</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">poly(N-isopropylacrylamide-co-acrylamide)&#160;</td>
			<td style="width:204px;">Sigma-Aldrich, MO, USA</td>
			<td>738727</td>
			<td>MW=20,000, LCST=34-38 oC</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Silicon oil</td>
			<td style="width:204px;">Sigma-Aldrich, MO, USA</td>
			<td>378372</td>
			<td>Viscosity 350 cSt</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Pluoronic L64</td>
			<td style="width:204px;">Sigma-Aldrich, MO, USA</td>
			<td style="width:119px;">435449</td>
			<td>100 ppm poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)</td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;width:216px;">genipin</td>
			<td style="width:204px;">TimTec LLC, DE, USA</td>
			<td>ST080860</td>
			<td>Mw = 226.23;&#160;</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Magnetic nanoparticles (MNPs)</td>
			<td style="width:204px;">Micromod Inc, Germany</td>
			<td>79-00-102</td>
			<td>nanomag-D-spio, 100 nm</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">TR-BSA</td>
			<td style="width:204px;">Life Technologies, NY USA</td>
			<td>A23017</td>
			<td>Albumin from Bovine Serum (BSA), Texas Red conjugate</td>
		</tr>
	</tbody>
</table>

alternating magnetic field-responsive hybrid gelatin microgels for controlled drug release

sıkı bir şekilde kontrol, on-demand ilaç dağıtım sağlamak manyetik duyarlı nano / mikro-mühendislik biyomateryaller biyomedikal uygulamalarda akıllı yumuşak cihazların yeni tip olarak geliştirilmiştir. Manyetik açıdan karşılık veren ilaç verme sistemleri bir dizi kavramı çalışmalar ya da in vivo ön klinik uygulamalarda da in vitro kanıt ile arasında etkili sonuçlar göstermiştir, ancak klinik ortamlarda kullanımı hala yetersiz biyolojik uygunluk veya biyodegradasyon ile sınırlıdır. Ayrıca, mevcut platformların birçoğu uydurmaları için sofistike teknikler güveniyor. Son zamanlarda, fiziksel olarak üç boyutlu bir jelatin ağı içinde küçük bir bileşen olarak poli (N-isopropylacrylamide- CO -akrilamit) zincirden tutulmasıyla da biyolojik olarak parçalanabilen, jelatin esaslı termo-duyarlı mikrojelin imalat göstermiştir. Bu çalışmada, bir manyeto-t sağlayan bir biyolojik olarak parçalanabilir ilaç serbest bırakma plâtformu imal etmek için kolay bir yöntem sunmakhermally ilaç salımı tetiklenir. Bu değişen bir manyetik alan uygulama sistemi ile bağlantılı olarak, jelatin esaslı koloidal mikrojelleri olan süperparamanyetik demir oksit nano-tanecikleri ve termo-duyarlı polimerlerin dahil edilmesiyle elde edilmiştir.

Protokolü doğru gerçekleştirildiğinde, imal edilmiş mikro-j eller aralığı 20 um ila 5 um arasında (Şekil 1B, C) ​​&#39;de çapları ile iyi karakterize edilen küresel bir morfoloji ve kolloidal dispersiyon sergilemelidir. Floresan MNPS veya floresan BSA ya MNPS ya da uyuşturucu (bu çalışmada BSA) doğru mikrojelin (Şekil 1D) içinde kapalı olup olmadığını teyit etmek için kullanılabilir. Imal mikrojeller kararlı ve kolajenaz ...

Watch this Scientific Journal Video about Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release at JoVE.com

Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release

Kontrollü İlaç Release için Manyetik Alan-Duyarlı Hibrid Jelatin mikroj Alternatif

Biz manyeto-termal duyarlı bir biyolojik olarak parçalanabilen jelatin bazlı ilaç salım platformu imal etmek, basit bir yöntem mevcut. Bu değişen bir manyetik alan uygulama sistemi ile bağlantılı olarak, genipin ile çapraz bağlanmış küresel jelatin mikro ağ içinde süperparamanyetik demir oksit nano-tanecikleri ve poli (N-isopropylacrylamide- CO -akrilamit) eklenerek elde edildi.

Magnetically-responsive nano/micro-engineered biomaterials that enable a tightly controlled, on-demand drug delivery have been developed as new types of ...

alternating-magnetic-field-responsive-hybrid-gelatin-microgels-for

Research

JoVE Journal

Bioengineering

9.7K Görüntüleme.  Kent State University.  Biz manyeto-termal duyarlı bir biyolojik olarak parçalanabilen jelatin bazlı ilaç salım platformu imal etmek, basit bir yöntem mevcut. Bu değişen bir manyetik alan uygulama sistemi ile bağlantılı olarak, genipin ile çapraz bağlanmış küresel jelatin mikro ağ içinde süperparamanyetik demir oksit nano-tanecikleri ve poli (N-isopropylacrylamide- CO -akrilamit) eklenerek elde edildi. 

Video: Alternating Magnetic Field-Responsive Hybrid Gelatin Microgels for Controlled Drug Release

Magnetically-Assisted Remote Controlled Microcatheter Tip Deflection under Magnetic Resonance Imaging

X-ray fluoroscopy-guided endovascular procedures have several significant limitations, including difficult catheter navigation and use of ionizing radiation, which can potentially be overcome using a magnetically steerable catheter under MR guidance.
	The main goal of this work is to develop a microcatheter whose tip can be remotely controlled using the magnetic field of the MR scanner. This protocol aims to describe the procedures for applying current to the microcoil-tipped microcatheter to produce consistent and controllable deflections.
	A microcoil was fabricated using laser lathe lithography onto a polyimide-tipped endovascular catheter. In vitro testing was performed in a waterbath and vessel phantom under the guidance of a 1.5-T MR system using steady-state free precession (SSFP) sequencing. Various amounts of current were applied to the coils of the microcatheter to produce measureable tip deflections and navigate in vascular phantoms.
	The development of this device provides a platform for future testing and opportunity to revolutionize the endovascular interventional MRI environment.

Current applied to an endovascular microcatheter with microcoil tip made by laser lathe lithography can achieve controllable deflections under magnetic resonance (MR) guidance, which may improve speed and efficacy of navigation of vasculature during various endovascular procedures.

Manyetik Rezonans Görüntüleme altında Manyetik Destekli Uzaktan Kumandalı mikrokateter İpucu Sehim

X-ray fluoroscopy-guided  endovascular procedures have several significant limitations, including  difficult catheter navigation and use of ionizing ...

Biyomühendislik

Characteristics of Precipitation-formed Polyethylene Glycol Microgels Are Controlled by Molecular Weight of Reactants

This work describes the formation of poly(ethylene glycol) (PEG) microgels via a photopolymerized precipitation reaction. Precipitation reactions offer several advantages over traditional microsphere fabrication techniques. Contrary to emulsion, suspension, and dispersion techniques, microgels formed by precipitation are of uniform shape and size, i.e.&#160;low polydispersity index, without the use of organic solvents or stabilizers. The mild conditions of the precipitation reaction, customizable properties of the microgels, and low viscosity for injections make them applicable for in vivo purposes. Unlike other fabrication techniques, microgel characteristics can be modified by changing the starting polymer molecular weight. Increasing the starting PEG molecular weight increased microgel diameter and swelling ratio. Further modifications are suggested such as encapsulating molecules during microgel crosslinking. Simple adaptations to the PEG microgel building blocks are explored for future applications of microgels as drug delivery vehicles and tissue engineering scaffolds.

This work describes the formation of poly(ethylene glycol) (PEG) microgels via a photopolymerized precipitation reaction. Increasing the PEG molecular weight increased microgel diameter and swelling ratio. Simple adaptations to the PEG microgel precipitation reaction are explored for future applications of microgels as drug delivery vehicles and tissue engineering scaffolds.

Yağış oluşturulmuş polietilen glikol mikrojellerinin özellikleri reaktiflerin molekül ağırlığı ile kontrol edilir

This work describes the formation of poly(ethylene glycol) (PEG) microgels via a photopolymerized precipitation reaction. Precipitation reactions offer ...

Hybrid &#181;CT-FMT imaging and image analysis

Fluorescence-mediated tomography (FMT) enables longitudinal and quantitative determination of the fluorescence distribution in vivo and can be used to assess the biodistribution of novel probes and to assess disease progression using established molecular probes or reporter genes. The combination with an anatomical modality, e.g., micro computed tomography (&#181;CT), is beneficial for image analysis and for fluorescence reconstruction. We describe a protocol for multimodal &#181;CT-FMT imaging including the image processing steps necessary to extract quantitative measurements. After preparing the mice and performing the imaging, the multimodal data sets are registered. Subsequently, an improved fluorescence reconstruction is performed, which takes into account the shape of the mouse. For quantitative analysis, organ segmentations are generated based on the anatomical data using our interactive segmentation tool. Finally, the biodistribution curves are generated using a batch-processing feature. We show the applicability of the method by assessing the biodistribution of a well-known probe that binds to bones and joints.

Hybrid  &#181;CT-FMT imaging and image analysis

We describe a protocol for hybrid imaging, combining fluorescence-mediated tomography (FMT) with micro computed tomography (&#181;CT). After fusion and reconstruction, we perform interactive organ segmentation to extract quantitative measurements of the fluorescence distribution.

Hibrid uCT-FMT görüntüleme ve görüntü analizi

Fluorescence-mediated tomography (FMT) enables longitudinal and quantitative determination of the fluorescence distribution in vivo and can be used to ...

Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect resulting in significant reductions in systemic toxicity. Nonetheless, insufficient release of encapsulated drug from liposomes has limited their clinical efficacy. Temperature-sensitive liposomes have been engineered to provide site-specific release of drug in order to overcome the problem of limited tumor drug bioavailability. Our lab has designed and developed a heat-activated thermosensitive liposome formulation of cisplatin (CDDP), known as HTLC, to provide triggered release of CDDP at solid tumors. Heat-activated delivery in vivo was achieved in murine models using a custom-built laser-based heating apparatus that provides a conformal heating pattern at the tumor site as confirmed by MR thermometry (MRT). A fiber optic temperature monitoring device was used to measure the temperature in real-time during the entire heating period with online adjustment of heat delivery by alternating the laser power. Drug delivery was optimized under magnetic resonance (MR) image guidance by co-encapsulation of an MR contrast agent (i.e.,&#160;gadoteridol) along with CDDP into the thermosensitive liposomes as a means to validate the heating protocol and to assess tumor accumulation. The heating protocol consisted of a preheating period of 5 min prior to administration of HTLC and 20 min heating post-injection. This heating protocol resulted in effective release of the encapsulated agents with the highest MR signal change observed in the heated tumor in comparison to the unheated tumor and muscle. This study demonstrated the successful application of the laser-based heating apparatus for preclinical thermosensitive liposome development and the importance of MR-guided validation of the heating protocol for optimization of drug delivery.

AN MRI-compatible&#160;custom-designed laser-based heating apparatus has been developed to provide local heating of subcutaneous tumors in order to activate release of agents from thermosensitive liposomes specifically at the tumor region.

Manyetik Rezonans Görüntü Rehberlik ile Termosensitif Lipozomlu gelen Sisplatinin Tetikleme Release için özel tasarlanmış Lazer-bazlı ısıtma Aparatı

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect ...

Composite Scaffolds of Interfacial Polyelectrolyte Fibers for Temporally Controlled Release of Biomolecules

Various scaffolds used in tissue engineering require a controlled biochemical environment to mimic the physiological cell niche. Interfacial polyelectrolyte complexation (IPC) fibers can be used for controlled delivery of various biological agents such as small molecule drugs, cells, proteins and growth factors. The simplicity of the methodology in making IPC fibers gives flexibility in its application for controlled biomolecule delivery. Here, we describe a method of incorporating IPC fibers into two different polymeric scaffolds, hydrophilic polysaccharide and hydrophobic polycaprolactone, to create a multi-component composite scaffold. We showed that IPC fibers can be easily embedded into these polymeric structures, enhancing the capability for sustained release and improved preservation of biomolecules. We also created a composite polymeric scaffold with topographical cues and sustained biochemical release that can have synergistic effects on cell behavior. Composite polymeric scaffolds with IPC fibers represent a novel and simple method of recreating the cellular niche.

Scaffolds for tissue engineering need to recapitulate the complex biochemical and biophysical microenvironment of the cellular niche. Here, we show the use of interfacial polyelectrolyte complexation fibers as a platform to create composite, multi-component polymeric scaffolds with sustained biochemical release.

Biyomoleküllerin Geçici olarak Kontrollü Release için Yüzey Polielektrolit Elyaf Kompozit Yapı iskeleleri

Various scaffolds used in tissue engineering require a controlled biochemical environment to mimic the physiological cell niche. Interfacial ...

Magnetic and Thermal-sensitive Poly(N-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were designed and fabricated for magnetically triggered release. PNIPAAm-based magnetic microgels with a spherical structure were produced via a temperature-induced emulsion followed with physical-crosslinking by mixing PNIPAAm, polyethylenimine (PEI), and Fe3O4-NH2 magnetic nanoparticles. Because of their dispersity, the Fe3O4-NH2 nanoparticles were embedded inside the polymer matrix. The amine groups exposed on the Fe3O4-NH2 and PEI surface supported the spherical structure by physically crosslinking with the amide groups of the PNIPAAm. The hydrophobic anti-cancer drug curcumin can be dispersed in water after encapsulation into the microgels. The microgels were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectral analysis. Furthermore, magnetically triggered release was studied under an external high frequency magnetic field (HFMF). A significant &#34;burst release&#34; of curcumin was observed after applying the HFMF to the microgels due to the magnetic inductive heating (hyperthermia) effect. This manuscript describes the magnetically triggered controlled release of Cur-PNIPAAm/Fe3O4-NH2 encapsulated curcumin, which can be potentially applied for tumor therapy.

Magnetic and Thermal-sensitive PolyN-isopropylacrylamide-based Microgels for Magnetically Triggered Controlled Release

This manuscript describes the preparation of magnetic and thermal-sensitive microgels via a temperature-induced emulsion without chemical reaction. These sensitive microgels were synthesized by mixing poly(N-isopropylacrylamide) (PNIPAAm), polyethylenimine (PEI) and Fe3O4-NH2 nanoparticles for the potential use in magnetically and thermally triggered drug-release.

Manyetik ve Termal Duyarlı Poli (<em&gt; K</em&gt; -izopropilakrilamid) Esaslı Manyetik Tetiklemeli Kontrollü Salınım İçin Mikrojeller

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were ...

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Regulation of chromatin compaction is an important process that governs gene expression in higher eukaryotes. Although chromatin compaction and gene expression regulation are commonly disrupted in many diseases, a locus-specific, endogenous, and reversible method to study and control these mechanisms of action has been lacking. To address this issue, we have developed and characterized novel gene-regulating bifunctional molecules. One component of the bifunctional molecule binds to a DNA-protein anchor so that it will be recruited to an allele-specific locus. The other component engages endogenous cellular chromatin-modifying machinery, recruiting these proteins to a gene of interest. These small molecules, called chemical epigenetic modifiers (CEMs), are capable of controlling gene expression and the chromatin environment in a dose-dependent and reversible manner. Here, we detail a CEM approach and its application to decrease gene expression and histone tail acetylation at a Green Fluorescent Protein (GFP) reporter located at the Oct4 locus in mouse embryonic stem cells (mESCs). We characterize the lead CEM (CEM23) using fluorescent microscopy, flow cytometry, and chromatin immunoprecipitation (ChIP), followed by a quantitative polymerase chain reaction (qPCR). While the power of this system is demonstrated at the Oct4 locus, conceptually, the CEM technology is modular and can be applied in other cell types and at other genomic loci.

Regulation of the chromatin environment is an essential process required for proper gene expression. Here, we describe a method for controlling gene expression through the recruitment of chromatin-modifying machinery in a gene-specific and reversible manner.

Kimyasal epigenetik değiştiriciler ile hücresel makine yeniden yönlendirerek Gen transkripsiyonu bastırmak

Regulation of chromatin compaction is an important process that governs gene expression in higher eukaryotes. Although chromatin compaction and gene ...

Use of High-Throughput Automated Microbioreactor System for Production of Model IgG1 in CHO Cells

Automated microscale bioreactors (15 mL) can be a useful tool for cell culture engineers. They facilitate the simultaneous execution of a wide variety of experimental conditions while minimizing potential process variability. Applications of this approach include: clone screening, temperature and pH shifts,&#160;media and supplement optimization. Furthermore, the small reactor volumes are conducive to large Design of Experiments that investigate a wide range of conditions. This allows upstream processes to be significantly optimized before scale-up where experimentation is more limited in scope due to time and economic constraints. Automated microscale bioreactor systems offer various advantages over traditional small scale cell culture units, such as shake flasks or spinner flasks. However, during pilot scale process development&#160;significant care must be taken to ensure that these advantages are realized. When run with care, the system can enable high level automation, can be programmed to run DOE&#39;s with a higher number of variables&#160;and can reduce sampling time when integrated with a nutrient analyzer or cell counter. Integration of the expert-derived heuristics presented here, with current automated microscale bioreactor experiments can minimize common pitfalls that hinder meaningful results. In the extreme, failure to adhere to the principles laid out here can lead to equipment damage that requires expensive repairs. Furthermore, the microbioreactor systems have small culture volumes&#160;making characterization of cell culture conditions difficult. The number and amount of samples taken in-process in batch mode culture is limited as operating volumes cannot fall below 10 mL. This method will discuss the benefits and drawbacks of microscale bioreactor systems.

A detailed protocol for the concurrent operation of 48 parallel cell cultures under varied conditions in a microbioreactor system is presented. Cell culture process, harvest and subsequent antibody titer analysis are described.

Yüksek üretilen iş kullanımı otomatik Microbioreactor sistemi modeli Igg1 CHO hücrelerdeki imalatı için

Automated microscale bioreactors (15 mL) can be a useful tool for cell culture engineers. They facilitate the simultaneous execution of a wide variety of ...

Wet-spinning-based Molding Process of Gelatin for Tissue Regeneration

This article presents an inexpensive method to fabricate gelatin, as a natural polymer, into monofilament fibers or other appropriate forms. Through the wet spinning method, gelatin fibers are produced by smooth extrusion in a suitable coagulation medium. To increase the functional surface of these gelatin fibers and their ability to mimic the features of tissues, gelatin can be molded into a tube form by referring to this concept. Examined by in vitro and in vivo tests, the gelatin tubes demonstrate a great potential for application in tissue engineering. Acting as a suitable filling gap material, gelatin tubes can be used to substitute the tissue in the damaged area (e.g., in the nervous or cardiovascular system), as well as to promote regeneration by providing a direct replacement of stem cells and neural circuitry. This protocol provides a detailed procedure for creating a biomaterial based on a natural polymer, and its implementation is expected to greatly benefit the development of correlative natural polymers, which help to realize tissue regeneration strategies.

We developed and describe a protocol based on the wet spinning concept, for the construction of gelatin-based biomaterials used for the application of tissue engineering.

Islak eğirme esaslı kalıplama işlemi doku rejenerasyonu için jelatin

This article presents an inexpensive method to fabricate gelatin, as a natural polymer, into monofilament fibers or other appropriate forms. Through the ...

Primary Clarification of CHO Harvested Cell Culture Fluid using an Acoustic Separator

Primary clarification is an essential step in a biomanufacturing process for the initial removal of cells from therapeutic products within the harvested cell culture fluid. While traditional methods like centrifugation or filtration are widely implemented for cell removal, the equipment for these processes have large footprints and operation can involve contamination risks and filter fouling. Additionally, traditional methods may not be ideal for continuous bioprocessing schemes for primary clarification. Thus, an alternate application using acoustic (sound) waves was investigated to continuously separate cells from the cell culture fluid. Presented in this study is a detailed protocol for using a bench-scale acoustic wave separator (AWS) for the primary separation of culture fluid containing a monoclonal IgG1 antibody from a CHO cell bioreactor harvest. Representative data are presented from the AWS and demonstrate how to achieve effective cell clarification and product recovery. Finally, potential applications for AWS in continuous bioprocessing are discussed. Overall, this study provides a practical and general protocol for the implementation of AWS in primary clarification for CHO cell cultures and further describes its application potential in continuous bioprocessing.

Presented here is a protocol for the primary clarification of CHO cell culture using an acoustic separator. This protocol can be used for the primary clarification of shake flask cultures or bioreactor harvests and has the potential application for continuous clarification of the cell bleed material during perfusion bioreactor operations.

Akustik Ayırıcı Kullanarak CHO Hasat Edilen Hücre Kültürü Sıvısının Birincil Netleştirilmesi

Primary clarification is an essential step in a biomanufacturing process for the initial removal of cells from therapeutic products within the harvested ...

Kontrollü İlaç Release için Manyetik Alan-Duyarlı Hibrid Jelatin mikroj Alternatif

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