This study was supported by the grant from AACP New Pharmacy Faculty Research Award Program, Medical Research Foundation of Oregon New Investigator Grant, Oregon State University-Startup fund, and Pacific University, School of Pharmacy Start-up fund.

1. إعداد الفرد ومتعدد المخدرات المذيلات تحميلها بواسطة طريقة الصب المذيبات <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> تزن خارج DTX 1 ملغ أو EVR 1 ملغ أو كليهما المخدرات في 1 ملغ لكل من المذيلات المخدرات المزدوجة (DDM). </li><li style=";text-align:right;direction:rtl"> تزن من 15 ملغ من PEG 2000 - ب -PLA 1800 أو PEG 4000 - 2200 ب -PLA لأي فرد أو DDM. </li><li style=";text-align:right;direction:rtl"> حل المخدرات / المخدرات والبوليمر في 0.5 مل من الأسيتونتريل ومكان في 5 مل قارورة أسفل جولة. </li><li style=";text-align:right;direction:rtl"> تشكيل رقيقة توزيع المخدرات فيلم البوليمر عن طريق تبخير هذا الدواء (ق) -polymer حل الأسيتونتريل تحت ضغط منخفض باستخدام المبخر الدوار. تعيين المبخر الدوار إلى 100 ​​دورة في الدقيقة، ودرجة حرارة حمام الماء 40 درجة مئوية وضغط الفراغ من 260 مليبار لمدة 5 دقائق تليها الحد إلى 100 ​​مليبار لمدة 3 دقائق أكثر. </li><li style=";text-align:right;direction:rtl"> ترطيب الفيلم المخدرات البوليمر مع 0.5 مل من الماء منزوع الأيونات في 50 درجة مئوية ويهز بلطف القارورة لتشكيل المذيلات. </li><li style=";text-align:right;direction:rtl"> تصفية نتيجةجي الحل micellar من خلال مرشح النايلون 0،2 ميكرون لإزالة أي الذائبة الامم المتحدة للمخدرات أو الملوثات في أنبوب 1.5 مل الطرد المركزي. </li></ol> 2. تقييم تحميل المخدرات والاستقرار في المذيلات عن طريق عكس مرحلة عالية الأداء اللوني السائل (RP-HPLC) <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> إجراء تحليل RP-HPLC مع عمود C8 equilibriated في 40 ° C في وضع isocratic مع الطور المتحرك من الأسيتونتريل / المياه (62/38) تحتوي على 0.1٪ حامض الفوسفوريك و1٪ الميثانول بمعدل تدفق من 1 مل / دقيقة و وحدة تخزين حقن 10 ميكرولتر. </li><li style=";text-align:right;direction:rtl"> تمييع الطازجة المذيلات (القسم 1) 1: 100 في الطور المتحرك قبل تحليل بواسطة RP-HPLC لتحديد الأولي تحميل المخدرات. متجر المذيلات الفردية غير مخفف وDDM في درجة حرارة الغرفة (25 درجة مئوية) لمدة 48 ساعة وإعداد الطازجة 1: 100 عينة مخففة في الطور المتحرك إلى إعادة تقييم من قبل RP-HPLC وتحديد المخدرات (ق) الاستقرار في المذيلات أكثر من 24 ساعة. </li><li style=";text-align:right;direction:rtl"> مراقبة DTX وEVR قمم في 227 و 279 نانومتر على التواليمع الاحتفاظ مرات من 1.7 و 5.7 دقيقة على التوالي. أداء جميع القياسات في ثلاث نسخ. البيانات الحالية كما تحميل يعني ± SD المخدرات. </li></ol> 3. تقييم مذيلة حجم الجسيمات التي تشتت الضوء الحيوي (DLS) <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> تمييع الطازجة المذيلات (كما هو موضح في القسم 1) في الماء منزوع الأيونات في نسبة 01:20 لتسفر عن تركيز البوليمر النهائي من 1.5 ملغ / مل. </li><li style=";text-align:right;direction:rtl"> قياس كثافة وني الليزر (633 نانومتر) في 173 درجة لتحديد نثر. أداء جميع القياسات في 25 ° C التالية قبل الموازنة لمدة 2 دقيقة. </li><li style=";text-align:right;direction:rtl"> أداء جميع القياسات في ثلاث نسخ. البيانات الحالية كما يعني Z-متوسط ​​حجم ± SD جنبا إلى جنب مع مؤشر التشتت المتعدد (PDI) للتوزيع. </li></ol> تقييم 4. في المختبر المخدرات بيان من فرد المذيلات وDDM <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> إعداد المذيلات الفردية وDDM كما هو موضح في القسم 1. تحميل 2.5 مل من المذيلات إلى شريط 3 مل غسيل الكلى معالوزن الجزيئي قطع (MWCO) من 7000 غ / مول. ملاحظة: تم اختيار هذا MWCO لتمكين المخدرات مجانية (ق) جنبا إلى جنب مع جزيئات البوليمر غير المصاحب لنزع فتيل بحرية من الكاسيت وبالتالي ضمان ظروف الحوض. </li><li style=";text-align:right;direction:rtl"> وضع أشرطة في 2.5 L من 10 ملي درجة الحموضة 7.4 العازلة الفوسفات (عن طريق تمييع الأسهم 200 ملي حل أعدت) وتغيير المخزن المؤقت كل ساعة 3 لضمان ظروف الحوض. الحفاظ على درجة حرارة المخزن المؤقت في 37 درجة مئوية طوال مدة التجربة. </li><li style=";text-align:right;direction:rtl"> في 0، 0.5، 1، 2، 3، 6، 9، 12، 24، و 48 ساعة، سحب 150 ميكرولتر من الحل في الكاسيت واستبدالها مع 150 ميكرولتر من العازلة الطازجة. </li><li style=";text-align:right;direction:rtl"> تحليل العينات باستخدام RP-HPLC النحو المنصوص عليه في الباب 2 لتحديد تركيز الدواء. منحنى تناسب المخدرات (ق) عن بيانات على أساس نموذج الانتشار البسيط مع جمعية المرحلة الأولى الأسي باستخدام برنامج stastitical. </li><li style=";text-align:right;direction:rtl"> حساب الوقت اللازم للوصول إلى 50٪ من الافراج عن المخدرات (ر 1/2) من البريدمنظمة العمل ضد الجوع المخدرات في المذيلات الفردية أو DDM على أساس منحنى المناسب. أداء جميع القياسات في أربعة توائم. </li></ol>

<ol>
	<li>Yokoyama, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polymeric+micelles+as+a+new+drug+carrier+system+and+their+required+considerations+for+clinical+trials.">Polymeric micelles as a new drug carrier system and their required considerations for clinical trials.</a> Expert Opin Drug Deliv. 7, 145-158 (2010).</li><li>Shin, H. C., Alani, A. W., Rao, D. A., Rockich, N. C., Kwon, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multi-drug+loaded+polymeric+micelles+for+simultaneous+delivery+of+poorly+soluble+anticancer+drugs.">Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs.</a> J Control Release. 140, 294-300 (2009).</li><li>Adams, M. L., Lavasanifar, A., Kwon, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amphiphilic+block+copolymers+for+drug+delivery.">Amphiphilic block copolymers for drug delivery.</a> J Pharm Sci. 92, 1343-1355 (2003).</li><li>Oerlemans, 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=Polymeric+micelles+in+anticancer+therapy:+targeting,+imaging+and+triggered+release.">Polymeric micelles in anticancer therapy: targeting, imaging and triggered release.</a> Pharm Res. 27, 2569-2589 (2010).</li><li>Shin, H. 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=A+3-in-1+polymeric+micelle+nanocontainer+for+poorly+water-soluble+drugs.">A 3-in-1 polymeric micelle nanocontainer for poorly water-soluble drugs.</a> Mol Pharm. 8, 1257-1265 (2011).</li><li>Hasenstein, J. R., 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=Antitumor+activity+of+Triolimus:+a+novel+multidrug-loaded+micelle+containing+Paclitaxel+Rapamycin,+and+17-AAG.">Antitumor activity of Triolimus: a novel multidrug-loaded micelle containing Paclitaxel Rapamycin, and 17-AAG.</a> Mol Cancer Ther. 11, 2233-2242 (2012).</li><li>Mazzaferro, S., 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=Bivalent+sequential+binding+of+docetaxel+to+methyl-beta-cyclodextrin.">Bivalent sequential binding of docetaxel to methyl-beta-cyclodextrin.</a> Int J Pharm. 416, 171-180 (2011).</li><li>Iwase, Y., Maitani, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparation+and+in+vivo+evaluation+of+liposomal+everolimus+for+lung+carcinoma+and+thyroid+carcinoma.">Preparation and in vivo evaluation of liposomal everolimus for lung carcinoma and thyroid carcinoma.</a> Biol Pharm Bull. 35, 975-979 (2012).</li><li>Mishra, G. P., Doddapaneni, B. S., Nguyen, D., Alani, A. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antiangiogenic+effect+of+docetaxel+and+everolimus+as+individual+and+dual-drug-loaded+micellar+nanocarriers.">Antiangiogenic effect of docetaxel and everolimus as individual and dual-drug-loaded micellar nanocarriers.</a> Pharm Res. 31, 660-669 (2014).</li><li>Xu, W., Ling, P., Zhang, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polymeric+micelles,+a+promising+drug+delivery+system+to+enhance+bioavailability+of+poorly+water-soluble+drugs.">Polymeric micelles, a promising drug delivery system to enhance bioavailability of poorly water-soluble drugs.</a> J Drug Deliv. 2013, 340315 (2013).</li><li>Lavasanifar, A., Samuel, J., Kwon, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Poly(ethylene+oxide)-block-poly(L-amino+acid)+micelles+for+drug+delivery.">Poly(ethylene oxide)-block-poly(L-amino acid) micelles for drug delivery.</a> Adv Drug Deliv Rev. 54, 169-190 (2002).</li></ol>

The authors have nothing to disclose.

The use of polymeric micelles for drug delivery continues to expand due to their versatility and ability to deliver hydrophobic drugs for various disease states. Therefore, the techniques needed to prepare and characterize these formulations prior to use in cell culture or animals is a critical first step to determine the best pairing between the drug and the polymer. PEG-b-PLA are excellent amphiphilic block copolymers for drug delivery purposes. However, the block length of the hydrophilic and hydrophobic s...

يمكن بوليمرات كتلة محبة للجهتين مع تكرار بنية مؤلفة من المجالات المائية وغير المائية بشكل عفوي التجمع الذاتي لتشكيل ثلاثة مجالس الجزيئات الأبعاد المعروفة باسم المذيلات البوليمرية. هذه الهياكل الأساسية لها مسعور الداخلي محاطة قذيفة ماء. جوهر مسعور لديه القدرة على دمج العقاقير مسعور إما عن طريق فخ المادي من خلال التفاعلات مسعور أو عن طريق الاقتران الكيميائية إلى العمود الفقري البوليمر. وتوجد العديد من 1 المزايا لاستخدام هذه بوليمرات كتلة لتشكيل المذيلات لتسليم المخدرات. وتشمل هذه إدماج المخدرات ضعيفة الذوبان، وتحسين الدوائية من الأدوية مسجلة، وتوافق مع الحياة و/ أو التحلل البيولوجي للبوليمرات يجعلها بديل آمن للمساعدات الانحلال التقليدية. 2 ميزة أخرى لاستخدام المذيلات البوليمر هي من الغروية حجم الجسيمات، بين 15- 150 نانومتر 3، مما يجعلها جذابة للسلطة الفلسطينيةتسليم renteral. لذلك، على مدى السنوات ال 20 الماضية ظهرت المذيلات البوليمرية كما نظم لتقديم الأدوية قابلة للسيئة المخدرات للذوبان في الماء وخاصة لعلاج السرطان. 3،4 حاليا هناك خمسة تركيبات micellar البوليمرية لعلاج السرطان الذين يخضعون التجارب السريرية. 4 أربعة من المذيلات في التجارب السريرية وبوليمرات diblock تستند PEG-في حين أن الأخير هو من البوليمرات triblock تحتوي على polyethyleneoxide. حجم هذه المذيلات تفاوتت من 20 نانومتر إلى 85 نانومتر. وميزة استخدام البوليمرات PEG تستند هي توافق مع الحياة، ويمكن أن يتوقف على الكتلة الثانية أيضا أن تكون قابلة للتحلل. وقد وضعت مؤخرا نظم لتقديم الأدوية الجديدة على أساس كتلة polyethyleneglycol- حمض -polylactic (PEG- ب -PLA) المذيلات البوليمرية لتسليم المتزامنة من الأدوية المضادة للسرطان متعددة. والمذيلات PEG- ب- جيش التحرير الشعبى الصينى على حد سواء حيويا والقابلة للتحلل. وقد أظهرت هذه المذيلات تحميل كما متعددة من المخدراتتثبيط ynergistic نماذج سرطانات مختلفة في المختبر والمجراة 2،5،6 وتنسجم مع النموذج الحالي لاستخدام أدوية متعددة في العلاج الكيميائي لمنع المقاومة وخفض سمية. ولذلك، فإن هناك قدرا كبيرا من الاهتمام في إعداد وتوصيف هذه الأنظمة تسليم المخدرات micellar للاستخدام في حالات السرطان والحالات المرضية الأخرى. في العمل دون ذكرناها عملية خطوة بخطوة التي تلك المذيلات يمكن إعداد وتميزت قبل تقييمها في الحالات المرضية من الفائدة. لغرض هذا العمل اثنين سيئة للذوبان وكلاء المضادة للسرطان، وقد تم اختيار DOCETAXEL (دي تي) وeverolimus (EVR). كلا DTX وEVR هي مركبات قابلة للذوبان في الماء سيئة مع الذوبان المياه الجوهرية في 1.9 و 9.6 ميكروغرام / مل على التوالي. واستخدمت 7،8 اثنين PEG- البوليمرات ب -PLA مع الأوزان الجزيئية المختلفة في هذا البروتوكول لبنات البناء لصياغة البوليمر المذيلات،هذه البوليمرات هي PEG 2000 - ب -PLA 1800 (3800 دا) وPEG 4000 - ب -PLA 2200 (6200 دا). وبالتالي يمكن PEG- المذيلات ب -PLA توفير منصة فريدة من نوعها باعتبارها nanocarrier لDTX وEVR فرادى ومجتمعة. المطلوب الكواشف / المواد والمعدات اللازمة لإعداد وتوصيف يتم سرد هذه المذيلات في الجدول 1.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>PEG2000-b-PLA1800</td>
			<td>Advanced Polymer Materials, Inc</td>
			<td>6-01- PLA/2000</td>
			<td>PLA MW can be specified on ordering</td>
		</tr>
		<tr>
			<td>PEG4000-b-PLA2200</td>
			<td>Advanced Polymer Materials, Inc</td>
			<td>6-01- PLA/4000</td>
			<td>PLA MW can be specified on ordering</td>
		</tr>
		<tr>
			<td>Docetaxel</td>
			<td>LC Laboratories</td>
			<td>D-1000</td>
			<td>100 mg</td>
		</tr>
		<tr>
			<td>Everolimus</td>
			<td>LC Laboratories</td>
			<td>E-4040</td>
			<td>100 mg</td>
		</tr>
		<tr>
			<td>Acetonitrile</td>
			<td>EMD/VWR</td>
			<td>EM-AX0145-1</td>
			<td>HPLC grade; 4 L</td>
		</tr>
		<tr>
			<td>Round bottom flask&#160;</td>
			<td>Glassco/VWR</td>
			<td>89426-496</td>
			<td>5 mL</td>
		</tr>
		<tr>
			<td>RV 10 Control Rotary Evaporators</td>
			<td>IKA Works</td>
			<td>8025001</td>
			<td>Rotoevaporator</td>
		</tr>
		<tr>
			<td>Shimadzhu HPLC with DAD detector</td>
			<td>Shimadzhu</td>
			<td></td>
			<td>RP-HPLC</td>
		</tr>
		<tr>
			<td>Slide-a-lyzer dialysis casette MWCO 7000</td>
			<td>Thermo Scientific, Inc</td>
			<td>66370</td>
			<td>3 mL</td>
		</tr>
		<tr>
			<td>Phosphate buffer pH 7.4 200 mM</td>
			<td>VWR</td>
			<td>100190-870</td>
			<td>500 mL</td>
		</tr>
		<tr>
			<td>Malvern NanoZS</td>
			<td>Malvern Instruments, UK</td>
			<td></td>
			<td>DLS</td>
		</tr>
		<tr>
			<td>Nylon filter</td>
			<td>Acrodisc/VWR</td>
			<td>28143-242</td>
			<td>13 mm; 0.2&#181;M</td>
		</tr>
		<tr>
			<td>Phosphoric acid, NF</td>
			<td>Spectrum Chemical/VWR</td>
			<td>700000-626</td>
			<td>100 mL</td>
		</tr>
		<tr>
			<td>GraphPad Prism</td>
			<td><a href="http://www.graphpad.com/">www.graphpad.com</a></td>
			<td></td>
			<td>Analysis software</td>
		</tr>
		<tr>
			<td>Zorbax SB-C8 Rapid Resolution cartridge&#160;</td>
			<td>Agilent Technologies</td>
			<td>866953-906</td>
			<td>4.6 &#215;75mm, 3.5 micron</td>
		</tr>
	</tbody>
</table>

preparation and characterization of individual and multi-drug loaded physically entrapped polymeric micelles

يمكن بوليمرات كتلة محبة للجهتين مثل كتلة polyethyleneglycol- حمض -polylactic (PEG- ب PLA) التجمع الذاتي في المذيلات فوق تركيز micellar الحرجة الذين يشكلون النوى مسعور محاطة قذائف ماء في البيئات المائية. جوهر هذه المذيلات يمكن استخدامها لتحميل مسعور، والمخدرات، للذوبان في الماء سيئة مثل DOCETAXEL (دي تي) وeverolimus (EVR). توصيف منهجي لقدرات هيكل مذيلة والتحميل المخدرات مهمة قبل في المختبر والدراسات المجراة يمكن أن تتم. والهدف من هذا البروتوكول الموصوفة هنا هو توفير الخطوات اللازمة لتحقيق توصيف المنتجات micellar موحدة. DTX وEVR يكون الذوبان الجوهرية من 1.9 و 9.6 ميكروغرام / مل على التوالي إعداد هذه المذيلات يمكن تحقيقه من خلال صب المذيبات مما يزيد من الذوبان المائي لDTX وEVR إلى 1.86 و 1.85 ملغ / مل على التوالي. ثباتية الدواء في المذيلات حدة التقييمuated في درجة حرارة الغرفة أكثر من 48 ساعة يشير إلى أن 97٪ أو أكثر من الأدوية يتم الاحتفاظ في الحل. تم تقييم حجم مذيلة باستخدام تشتت الضوء الحيوي، وأشار إلى أن حجم هذه المذيلات كان أقل من 50 نانومتر، ويعتمد على الوزن الجزيئي للبوليمر. تم تقييم الافراج المخدرات من المذيلات باستخدام غسيل الكلى في ظل ظروف الحوض في درجة الحموضة 7.4 عند 37 درجة مئوية خلال 48 ساعة. وتشير النتائج منحنى المناسب أن الإفراج عن المخدرات يقودها عملية الدرجة الأولى مشيرا إلى أنه تم نشر مدفوعة.

DTX الفردي أو المذيلات EVR وDTX وEVR DDM في PEG- ب -PLA تصاغ المذيلات بنجاح في أي PEG 4000 - ب -PLA 2200 أو PEG 2000 - ب -PLA 1800 (الشكل 1). أظهر DTX، EVR، وDDM الاستقرار مماثل في PEG 4000 - ب -PLA 2200 أو PEG 2000...

Watch this Scientific Journal Video about Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles at JoVE.com

Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles

The goal of this protocol is to describe the preparation and characterization of physically entrapped, poorly water soluble drugs in micellar drug delivery systems composed of amphiphilic block copolymers.

إعداد وتوصيف الفردية والمتعددة المخدرات تحميل جسديا شرك البوليمرية المذيلات

Amphiphilic block copolymers like polyethyleneglycol-block-polylactic acid (PEG-b-PLA) can self-assemble into micelles above their critical micellar ...

preparation-characterization-individual-multi-drug-loaded-physically

Research

JoVE Journal

Chemistry

11.2K Views.  Pacific University. The goal of this protocol is to describe the preparation and characterization of physically entrapped, poorly water soluble drugs in micellar drug delivery systems composed of amphiphilic block copolymers.

Video: Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid phase by using combinatorial chemistry. One of the most well studied classes of peptidomimetics is peptoids. Peptoids are easy to synthesize and have been shown to be proteolysis-resistant and cell-permeable. Over the past decade, many useful protein ligands have been identified through screening of peptoid libraries. However, most of the ligands identified from peptoid libraries do not display high affinity, with rare exceptions. This may be due, in part, to the lack of chiral centers and conformational constraints in peptoid molecules. Recently, we described a new synthetic route to access peptide tertiary amides (PTAs). PTAs are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. With side chains on both &#945;-carbon and main chain nitrogen atoms, the conformation of these molecules are greatly constrained by sterical hindrance and allylic 1,3 strain. (Figure 1) Our study suggests that these PTA molecules are highly structured in solution and can be used to identify protein ligands. We believe that these molecules can be a future source of high-affinity protein ligands. Here we describe the synthetic method combining the power of both split-and-pool and sub-monomer strategies to synthesize a sample one-bead one-compound (OBOC) library of PTAs.

Peptide tertiary amides (PTAs) are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. Here we describe a synthetic method which combines&#160;both split-and-pool and sub-monomer strategies to synthesize a one-bead one-compound library of PTAs.

التجميعي تقسيم وبركة وتوصيف الببتيد المكتبة أميد العالي

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid ...

Synthesis and Characterization of Functionalized Metal-organic Frameworks

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and technological applications. Their signature property is their ultrahigh porosity, which however imparts a series of challenges when it comes to both constructing them and working with them. Securing desired MOF chemical and physical functionality by linker/node assembly into a highly porous framework of choice can pose difficulties, as less porous and more thermodynamically stable congeners (e.g., other crystalline polymorphs, catenated analogues) are often preferentially obtained by conventional synthesis methods. Once the desired product is obtained, its characterization often requires specialized techniques that address complications potentially arising from, for example, guest-molecule loss or preferential orientation of microcrystallites. Finally, accessing the large voids inside the MOFs for use in applications that involve gases can be problematic, as frameworks may be subject to collapse during removal of solvent molecules (remnants of solvothermal synthesis). In this paper, we describe synthesis and characterization methods routinely utilized in our lab either to solve or circumvent these issues. The methods include solvent-assisted linker exchange, powder X-ray diffraction in capillaries, and materials activation (cavity evacuation) by supercritical CO2 drying. Finally, we provide a protocol for determining a suitable pressure region for applying the Brunauer-Emmett-Teller analysis to nitrogen isotherms, so as to estimate surface area of MOFs with good accuracy.

Synthesis, activation, and characterization of intentionally designed metal-organic framework materials is challenging, especially when building blocks are incompatible or unwanted polymorphs are thermodynamically favored over desired forms. We describe how applications of solvent-assisted linker exchange, powder X-ray diffraction in capillaries and activation via supercritical CO2 drying, can address some of these challenges.

أطر توليف وتوصيف بين functionalized المعدنية العضوية

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and ...

Preparation and Characterization of SDF-1&#945;-Chitosan-Dextran Sulfate Nanoparticles

Chitosan (CS) and dextran sulfate (DS) are charged polysaccharides (glycans), which form polyelectrolyte complex-based nanoparticles when mixed under appropriate conditions. The glycan nanoparticles are useful carriers for protein factors, which facilitate the in vivo delivery of the proteins and sustain their retention in the targeted tissue. The glycan polyelectrolyte complexes are also ideal for protein delivery, as the incorporation is carried out in aqueous solution, which reduces the likelihood of inactivation of the proteins. Proteins with a heparin-binding site adhere to dextran sulfate readily, and are, in turn, stabilized by the binding. These particles are also less inflammatory and toxic when delivered in vivo. In the protocol described below, SDF-1&#945; (Stromal cell-derived factor-1&#945;), a stem cell homing factor, is first mixed and incubated with dextran sulfate. Chitosan is added to the mixture to form polyelectrolyte complexes, followed by zinc sulfate to stabilize the complexes with zinc bridges. The resultant SDF-1&#945;-DS-CS particles are measured for size (diameter) and surface charge (zeta potential). The amount of the incorporated SDF-1&#945; is determined, followed by measurements of its in vitro release rate and its chemotactic activity in a particle-bound form.

Preparation and Characterization of SDF-1&amp;#945;-Chitosan-Dextran Sulfate Nanoparticles

The objective of this protocol is to incorporate SDF-1&#945;, a stem cell homing factor, into dextran sulfate-chitosan nanoparticles. The resultant particles are measured for their size and zeta potential, as well as the content, activity, and in vitro release rate of SDF-1&#945; from the nanoparticles.

إعداد وتوصيف SDF-1α-الشيتوزان-ديكستران سلفات النانوية

Chitosan (CS) and dextran sulfate (DS) are charged polysaccharides (glycans), which form polyelectrolyte complex-based nanoparticles when mixed under ...

Synthesis and Characterization of Supramolecular Colloids

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical properties for applications in photonics, drug delivery and coating technology. Here we present a new family of colloidal building blocks, coined supramolecular colloids, whose self-assembly is controlled through surface-functionalization with a benzene-1,3,5-tricarboxamide (BTA) derived supramolecular moiety. Such BTAs interact via directional, strong, yet reversible hydrogen-bonds with other identical BTAs. Herein, a protocol is presented that describes how to couple these BTAs to colloids and how to quantify the number of coupling sites, which determines the multivalency of the supramolecular colloids. Light scattering measurements show that the refractive index of the colloids is almost matched with that of the solvent, which strongly reduces the van der Waals forces between the colloids. Before photo-activation, the colloids remain well dispersed, as the BTAs are equipped with a photo-labile group that blocks the formation of hydrogen-bonds. Controlled deprotection with UV-light activates the short-range hydrogen-bonds between the BTAs, which triggers the colloidal self-assembly. The evolution from the dispersed state to the clustered state is monitored by confocal microscopy. These results are further quantified by image analysis with simple routines using ImageJ and Matlab. This merger of supramolecular chemistry and colloidal science offers a direct route towards light- and thermo-responsive colloidal assembly encoded in the surface-grafted monolayer.

A protocol for the synthesis and characterization of colloids coated with supramolecular moieties is described. These supramolecular colloids undergo self-assembly upon the activation of the hydrogen-bonds between the surface-anchored molecules by UV-light.

توليف وتوصيف المواد الغروية Supramolecular

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical ...

Low-energy Cathodoluminescence for (Oxy)Nitride Phosphors

Nitride and oxynitride (Sialon) phosphors are good candidates for the ultraviolet and visible emission applications. High performance, good stability and flexibility of their emission properties can be achieved by controlling their composition and dopants. However, a lot of work is still required to improve their properties and to reduce the production cost. A possible approach is to correlate the luminescence properties of the Sialon particles with their local structural and chemical environment in order to optimize their growth parameters and find novel phosphors. For such a purpose, the low-voltage cathodoluminescence (CL) microscopy is a powerful technique. The use of electron as an excitation source allows detecting most of the luminescence centers, revealing their luminescence distribution spatially and in depth, directly comparing CL results with the other electron-based techniques, and investigating the stability of their luminescence properties under stress. Such advantages for phosphors characterization will be highlighted through examples of investigation on several Sialon phosphors by low-energy CL.

Low-energy Cathodoluminescence for OxyNitride Phosphors

An excellent chemical and luminescence stabilities of (oxy)nitride phosphors present it as an promising alternative to currently used sulfide and oxide phosphors. In this paper, we present the way to investigate its local luminescence properties using low-energy cathodoluminescence (CL).

Cathodoluminescence منخفضة الطاقة ل(أوكسي) الليومينيوفورات نتريد

Nitride and oxynitride (Sialon) phosphors are good candidates for the ultraviolet and visible emission applications. High performance, good stability and ...

Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins with the synthesis of a hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) homopolymer using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Under mild visible light irradiation (&#955; = 460 nm, 0.7 mW/cm2), this macro-chain transfer agent (macro-CTA) in the presence of a ruthenium based photoredox catalyst, Ru(bpy)3Cl2 can be chain extended with a second monomer to form a well-defined block copolymer in a process known as Photoinduced Electron Transfer RAFT (PET-RAFT). When PET-RAFT is used to chain extend POEGMA with benzyl methacrylate (BzMA) in ethanol (EtOH), polymeric nanoparticles with different morphologies are formed in situ according to a polymerization-induced self-assembly (PISA) mechanism. Self-assembly into nanoparticles presenting POEGMA chains at the corona and poly(benzyl methacrylate) (PBzMA) chains in the core occurs in situ due to the growing insolubility of the PBzMA block in ethanol. Interestingly, the formation of highly pure worm-like micelles can be readily monitored by observing the onset of a highly viscous gel in situ due to nanoparticle entanglements occurring during the polymerization. This process thereby allows for a more reproducible synthesis of worm-like micelles simply by monitoring the solution viscosity during the course of the polymerization. In addition, the light stimulus can be intermittently applied in an ON/OFF manner demonstrating temporal control over the nanoparticle morphology.

This article describes a process for producing polymeric self-assembled nanoparticles using visible light mediated dispersion polymerization. Using low energy visible light to control the polymerization allows for the reproducible formation of self-assembled worm-like micelles at high solids content.

توليف سطحي من المذيلات تشبه دودة من الضوء المرئي وساطة التشتت البلمرة عن طريق Photoredox محفز

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins ...

Anionic Polymerization of an Amphiphilic Copolymer for Preparation of Block Copolymer Micelles Stabilized by &#960;-&#960; Stacking Interactions

In this study, an amphiphilic copolymer that includes a core-forming block with phenyl groups was synthesized by living anionic polymerization of phenyl glycidyl ether (PheGE) on methoxy-polyethylene glycol (mPEG-b-PPheGE). Characterization of the copolymer revealed a narrow molecular distribution (PDI &#60; 1.03) and confirmed the degree of polymerization of mPEG122-b-(PheGE)15. The critical micelle concentration of the copolymer was evaluated using an established fluorescence method with the aggregation behavior evaluated by dynamic light scattering and transmission electronic microscopy. The potential of the copolymer for use in drug delivery applications was evaluated in a preliminary manner including in vitro biocompatibility, loading and release of the hydrophobic anti-cancer drug doxorubicin (DOX). A stable micelle formulation of DOX was prepared with drug loading levels up to 14% (wt%), drug loading efficiencies &#62; 60% (w/w) and sustained release of drug over 4 days under physiologically relevant conditions (acidic and neutral pH, presence of albumin). The high drug loading level and sustained release is attributed to stabilizing &#960;-&#960; interactions between DOX and the core-forming block of the micelles.

Anionic Polymerization of an Amphiphilic Copolymer for Preparation of Block Copolymer Micelles Stabilized by &amp;#960;-&amp;#960; Stacking Interactions

The key steps of living anionic polymerization of phenyl glycidyl ether (PheGE) on methoxy-polyethylene glycol (mPEG-b-PPheGE) are described. The resulting block copolymer micelles (BCMs) were loaded with doxorubicin 14% (wt%) and sustained release of drug over 4 days under physiologically relevant conditions was obtained.

أنيونية البلمرة من كوبوليمر محبة للجهتين لإعداد كتلة كوبوليمر المذيلات استقرت بواسطة تفاعلات التراص π-π

In this study, an amphiphilic copolymer that includes a core-forming block with phenyl groups was synthesized by living anionic polymerization of phenyl ...

Synthesis of Cyclic Polymers and Characterization of Their Diffusive Motion in the Melt State at the Single Molecule Level

We demonstrate a method for the synthesis of cyclic polymers and a protocol for characterizing their diffusive motion in a melt state at the single molecule level. An electrostatic self-assembly and covalent fixation (ESA-CF) process is used for the synthesis of the cyclic poly(tetrahydrofuran) (poly(THF)). The diffusive motion of individual cyclic polymer chains in a melt state is visualized using single molecule fluorescence imaging by incorporating a fluorophore unit in the cyclic chains. The diffusive motion of the chains is quantitatively characterized by means of a combination of mean-squared displacement (MSD) analysis and a cumulative distribution function (CDF) analysis. The cyclic polymer exhibits multiple-mode diffusion which is distinct from its linear counterpart. The results demonstrate that the diffusional heterogeneity of polymers that is often hidden behind ensemble averaging can be revealed by the efficient synthesis of the cyclic polymers using the ESA-CF process and the quantitative analysis of the diffusive motion at the single molecule level using the MSD and CDF analyses.

A protocol for the synthesis and characterization of diffusive motion of cyclic polymers at the single molecule level is presented.

توليف دوري البوليمرات وتوصيف تلك الحركة ناشر في الدولة تذوب في واحدة جزيء مستوى

We demonstrate a method for the synthesis of cyclic polymers and a protocol for characterizing their diffusive motion in a melt state at the single ...

Synthesis of Plant Phenol-derived Polymeric Dyes for Direct or Mordant-based Hair Dyeing

Effective hair dyeing through in situ incubation of keratin hair with the products of fungal laccase-catalyzed polymerization of plant phenols has been previously demonstrated. However, the dyeing process takes a long time to complete compared to commercial hair-dyeing products. To overcome this bottleneck, pre-synthesized polymeric products of the oxidative reaction of Trametes versicolor laccase on catechin and catechol, either with or without mordant agents (e.g., FeSO4), were here employed to achieve permanent keratin hair dyeing in various colors and shades. The laccase action in acidic sodium acetate buffer led to a deep black coloration after coupling reactions between the plant phenols. The colored dye products were then desalted and concentrated with ultrafiltration. The dyes, with or without mordant agents, caused a significant increase in &#916;E values (i.e., color difference value) in gray human hair within 2.5 hours. In addition, different keratin colors and shades were induced depending upon the mordanting and pH changes. The dyed hair also exhibited a strong resistance to detergent treatments, indicating that our methods can give rise to permanent hair dyeing.&#160;Overall, our work has provided novel insight into developing eco-friendly hair-dyeing methods as alternatives to commercial toxic diamine-based dyes.

Here, we present a protocol to use pre-synthesized polymeric products derived from fungal laccase-catalyzed polymerization of plant phenols, either with or without mordant agents (e.g., FeSO4), to induce detergent-resistant keratin hair dyeing within 2.5 hours.

توليف الأصباغ البوليمرية المستمدة الفينول النباتية للصباغة الشعر المباشرة أو استنادا لاذع،

Effective hair dyeing through in situ incubation of keratin hair with the products of fungal laccase-catalyzed polymerization of plant phenols has been ...

Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging

Paramagnetic complexes of gadolinium(III) with acyclic or macrocyclic chelates are the most commonly used contrast agents (CAs) for magnetic resonance imaging (MRI). Their purpose is to enhance the relaxation rate of water protons in tissue, thus increasing the MR image contrast and the specificity of the MRI measurements. Current clinically approved contrast agents are low molecular weight molecules that are rapidly cleared from the body. The use of dendrimers as carriers of paramagnetic chelators can play an important role in the future development of more efficient MRI contrast agents. Specifically, the increase in local concentration of the paramagnetic species results in a higher signal contrast. Furthermore, this CA provides a longer tissue retention time due to its high molecular weight and size. Here, we demonstrate a convenient procedure for the preparation of macromolecular MRI contrast agents based on poly(amidoamine) (PAMAM) dendrimers with monomacrocyclic DOTA-type chelators (DOTA &#8211; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate). The chelating unit was appended by exploiting the reactivity of the isothiocyanate (NCS) group towards the amine surface groups of the PAMAM dendrimer to form thiourea bridges. Dendrimeric products were purified and analyzed by means of nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis. Finally, high resolution MR images were recorded and the signal contrasts obtained from the prepared dendrimeric and the commercially available monomeric agents were compared.

Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging

This protocol describes the preparation and characterization of a dendrimeric magnetic resonance imaging (MRI) contrast agent that carries cyclen-based macrocyclic chelates coordinating paramagnetic gadolinium ions. In a series of MRI experiments in vitro, this agent produced an amplified MRI signal when compared to the commercially available monomeric analogue.

إعداد و<em&gt; في المختبر</em&gt; توصيف وكلاء التباين القائم Dendrimer للتصوير بالرنين المغناطيسي

Paramagnetic complexes of gadolinium(III) with acyclic or macrocyclic chelates are the most commonly used contrast agents (CAs) for magnetic resonance ...