CA acknowledges a Discovery grant from the Natural Sciences and Engineering Research Council of Canada. CA acknowledges a Chair in Pharmaceutics and Drug Delivery from GSK. The authors declare no competing financial interest.

<img alt="Figura 1" src="/files/ftp_upload/54422/54422fig1.jpg" /> Figura 1. Schema che mostra i nove passi chiave nella preparazione del MPEG-b -PPheGE copolimero. <a href="http://ecsource.jove.com/files/ftp_upload/54422/54422fig1large.jpg" target="_blank">Clicca qui per vedere una versione più grande di questa figura.</a> 1. Preparazione dei reagenti in condizioni asciutte <ol><li> Preparazione dei reagenti. <ol><li> Pesare 15 g di mPEG-5K...

<ol>
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Grazie al buon controllo che la polimerizzazione anionica fornisce più di peso molecolare è uno dei processi più applicati nell&#39;industria per la preparazione di polimeri a base di monomeri di ossirano (PEG e PPG). Le condizioni ottimali e stringenti devono essere utilizzati per la polimerizzazione di successo da raggiungere. la purificazione rigorosa di tutti i reagenti e apparecchi adeguata sono essenziali per il personaggio vivente della sintesi. Limitazioni della configurazione attuale sono per lo più associa...

In mezzi acquosi, copolimeri a blocchi anfifilici assemblare per formare micelle copolimero a blocchi di dimensioni nanometriche (BCMs) che consistono di un nucleo idrofobico circondato da un guscio idrofilo o corona. Il nucleo micelle può fungere da serbatoio per l&#39;incorporazione di farmaci idrofobi; mentre, la corona idrofila fornisce un&#39;interfaccia tra il nucleo e il mezzo esterno. Poli (etilene glicole) (PEG) e suoi derivati sono una delle più importanti classi di polimeri e uno dei più ampiamente utilizzato nella formulazione di droga. 1-3 BCMs hanno dimostrato di essere una piattaforma drug delivery degna con diverse formulazioni basandosi su questo tecnologia attualmente in sviluppo clinico fase avanzata. 4 più comunemente, il blocco idrofobo del copolimero comprende policaprolattone, poli (D, L-lattide), poli (ossido di propilene) o poli (β-benzil-L-aspartato). 5 -9 Il gruppo di Kataoka indagato micelle sferiche formate da sone B </em&gt; -PBLA E poli (ossido di etilene) - B -. (Polyaspartic doxorubicina acido-coniugato) per la consegna di doxorubicina (DOX) 10,11 Nelle loro relazioni, hanno messo in avanti che le interazioni π-¸ tra il farmaco di polimero coniugato o PBLA e gratuito DOX agire per stabilizzare il nucleo micelle con conseguente aumento di carico di droga e la ritenzione. È accertato che la compatibilità o le interazioni tra un farmaco e il blocco di formazione nucleo sono fattori determinanti di parametri chiave relativi alle prestazioni. 12 Oltre a DOX, una serie di terapie contro il cancro includono anelli aromatici all&#39;interno della loro struttura di base (ad esempio, metotrexate, Olaparib, SN -38). Come risultato vi è interesse significativo nella sintesi di copolimeri che comprendono anelli benzilici nei loro blocchi di formazione nucleo. Anionico anello apertura polimerizzazione di PEG e dei suoi derivati abilitare il controllo sul peso molecolare e il risultato in materiali di bassa polidispersità in buona resa. 13,14 di etileossido ne con etere fenil glicidil (PheGE) o ossido di stirene (SO) può essere (co) polimerizzare per formare copolimeri a blocchi che formano micelle per solubilizzazione dei farmaci idrofobi. 15-18 La presente relazione descrive i passi necessari per vivere polimerizzazione anionica di fenil glicidil etere monomero in mPEG-OH come macroinitiator (Figura 1). Il copolimero a blocchi risultante e gli aggregati sono quindi caratterizzati in termini di proprietà di rilevanza usare nella somministrazione di farmaci.

<table border="0" cellpadding="0" cellspacing="0" width="742">
	<colgroup>
		<col span="2" />
		<col />
		<col span="2" />
		<col />
		<col span="2" />
		<col />
	</colgroup>
	<tbody>
		<tr height="62">
			<td colspan="3" dir="LTR" height="62" style="height:62px;width:224px;">DMEM/HAMF12</td>
			<td colspan="3" style="width:227px;">Gibco, Life Technologies</td>
			<td colspan="2" style="width:125px;">12500</td>
			<td dir="LTR" style="width:171px;">Supplemented with 10%FBS. Warm in 37 &#176;C water bath 
			&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;</td>
		</tr>
		<tr height="20">
			<td colspan="3" height="20" style="height:20px;">Trypsin-EDTA(0.25%)</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">T4049</td>
			<td dir="LTR">Warm in 37 &#176;C water bath&#160;</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Fetal bovine serum (FBS)</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">F1051</td>
			<td dir="LTR">Canada origin</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">MDA-MB-468 cell line</td>
			<td colspan="3">ATCC</td>
			<td colspan="2">HTB-132</td>
			<td></td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">MTS tetrazolium reagent</td>
			<td colspan="3">PROMEGA</td>
			<td colspan="2">G111B</td>
			<td></td>
		</tr>
		<tr height="20">
			<td colspan="3" height="20" style="height:20px;">Phenazine ethosulfate (PES)</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">P4544</td>
			<td dir="LTR">&#62;95%</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">mPEG5K (Mn 5400 g/mol)</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">81323</td>
			<td>PDI=1.02</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Dimethylsolfoxide (DMSO)</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">D4540</td>
			<td dir="LTR">&#62;99.5%</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Naphthalene</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">147141</td>
			<td dir="LTR">&#62;99%</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Phenyl glycidyl ether</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">A32608</td>
			<td dir="LTR">&#62;85%</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Benzophenone</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">427551</td>
			<td dir="LTR">&#62;99%</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Potassium</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">451096</td>
			<td dir="LTR">&#62;98%</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Tetrahydrofuran</td>
			<td colspan="3">Caledon Laboratory Chemicals</td>
			<td colspan="2">8900 1</td>
			<td dir="LTR">ACS</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Hexane</td>
			<td colspan="3">Caledon Laboratory Chemicals</td>
			<td colspan="2">5500 1</td>
			<td dir="LTR">ACS</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Calcium hydride (CaH2)</td>
			<td colspan="3">ACP</td>
			<td colspan="2">C-0460</td>
			<td dir="LTR">&#62;99.5%</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Diethyl Ether</td>
			<td colspan="3">Caledon Laboratory Chemicals</td>
			<td colspan="2">1/10/4800</td>
			<td dir="LTR">ACS</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Microplate reader</td>
			<td colspan="3">BioTek Instruments</td>
			<td colspan="2"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Differential scanning calorimetry (DSC)</td>
			<td colspan="3">TA Instruments Inc</td>
			<td colspan="2">DSC Q100</td>
			<td></td>
		</tr>
		<tr height="32">
			<td colspan="3" dir="LTR" height="32" style="height:32px;">Gel permeation chromatography (GPC)</td>
			<td colspan="3">Waters</td>
			<td colspan="2" style="width:125px;">2695 separation moldule / 2414 detector&#160;</td>
			<td dir="LTR" style="width:171px;">2 Columns: Agilent Plgel 5&#181;m Mixed-D</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">NMR spectroscopy</td>
			<td colspan="3">Varian Mercury 400MHz</td>
			<td colspan="2"></td>
			<td></td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">Chloroform-d</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">151858</td>
			<td dir="LTR">99.96%</td>
		</tr>
		<tr height="20">
			<td colspan="3" dir="LTR" height="20" style="height:20px;">DMSO-d</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">156914</td>
			<td dir="LTR">99.96%</td>
		</tr>
		<tr height="20">
			<td colspan="3" height="20" style="height:20px;">Vaccum pump&#160;</td>
			<td colspan="3">Gardner Denver Welch Vacuum Tech, Inc.</td>
			<td colspan="2"></td>
			<td>Ultimate&#160; pressure 1.10-4 torr</td>
		</tr>
		<tr height="20">
			<td colspan="3" height="20" style="height:20px;">Drierit with indicator, 8 mesh</td>
			<td colspan="3">Sigma-Aldrich</td>
			<td colspan="2">238988</td>
			<td>Regenerated at 230&#176;C for 2 hrs</td>
		</tr>
	</tbody>
</table>

anionic polymerization of an amphiphilic copolymer for preparation of block copolymer micelles stabilized by &#960;-&#960; stacking interactions

In questo studio, un copolimero anfifilica che comprende un blocco di formazione nucleo con gruppi fenilici è stato sintetizzato da polimerizzazione anionica vivente di fenil glicidil etere (PheGE) on metossipolietilenglicole (MPEG-b -PPheGE). Caratterizzazione del copolimero rivelato una stretta distribuzione molecolare (PDI &lt;1.03) e confermato il grado di polimerizzazione di mPEG 122 - b - (PheGE) 15. La concentrazione critica micellare del copolimero è stata valutata utilizzando un metodo a fluorescenza stabilita con il comportamento di aggregazione valutate dalla dispersione della luce dinamica e trasmissione microscopia elettronica. Il potenziale del copolimero per l&#39;uso in applicazioni di consegna della droga è stata valutata in modo preliminare compreso in vitro biocompatibilità, caricamento e rilascio del idrofobico antitumorale doxorubicina farmaco (DOX). Una formulazione micelle stabile di DOX è stato preparato con i livelli di farmaco di carico fino al 14% (% in peso), carico di droga efficiper proiezione&gt; 60% (w / w) e sostenuta rilascio di farmaco per 4 giorni in condizioni fisiologicamente rilevanti (pH acido e neutro, presenza di albumina). Il livello elevato carico di droga e rilascio prolungato è attribuita alla stabilizzazione interazioni ¸-π tra DOX e il blocco di centro di formazione delle micelle.

<img alt="Figura 3" src="/files/ftp_upload/54422/54422fig3.jpg" /> Figura 3. Illustrazione della polimerizzazione anionica fenil glicidil etere sull&#39;MPEG macroinitiator produrre MPEG-b - (PheGE) 15 per la preparazione di micelle copolimero a blocchi per il caricamento di doxorubicina La rappresentazione la deprotonazione del gruppo ossidrile di mPEG utilizzando naftalene potassio.</s...

Watch this Scientific Journal Video about Anionic Polymerization of an Amphiphilic Copolymer for Preparation of Block Copolymer Micelles Stabilized by Ãâ‚¬-Ãâ‚¬ Stacking Interactions at JoVE.com

Anionic Polymerization of an Amphiphilic Copolymer for Preparation of Block Copolymer Micelles Stabilized by ÃƒÆ’Ã‚ÂÃƒÂ¢Ã¢â‚¬Å¡Ã‚Â¬-ÃƒÆ’Ã‚ÂÃƒÂ¢Ã¢â‚¬Å¡Ã‚Â¬ Stacking Interactions

Sono descritte le fasi cruciali di polimerizzazione anionica vivente di etere fenil glicidil (PheGE) di glicole metossi-polietilene (MPEG-b -PPheGE). Le micelle copolimero a blocchi risultanti (BCMS) sono stati caricati con doxorubicina 14% (% in peso) e rilascio prolungato di farmaci oltre 4 giorni sotto fisiologicamente è stato ottenuto relative condizioni.

Anionico polimerizzazione di un copolimero Amphiphilic per la preparazione di copolimero a blocchi micelle stabilizzata da π-¸ Interazioni Stacking

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

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JoVE Journal

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Chemistry

Organic Chemistry

Unit 1

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

Synthetic Polymers

Ethers, Epoxides, Sulfides

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Utilizzando Polystyrene-<em&gt; Blocco</em&gt; -poly (Acido acrilico) Rivestiti metallo Nanoparticelle come monomeri per loro omo- e co-polimerizzazione

We present a template-free method for &#8220;polymerizing&#8221; nanoparticles into long chains without side branches. A variety of nanoparticles are ...

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Preparazione e caratterizzazione di individuale e Multi-droga Loaded Fisicamente intrappolate polimerici Micelle

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

Facile Preparation of Internally Self-assembled Lipid Particles Stabilized by Carbon Nanotubes

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We present a facile method to prepare nanostructured lipid particles stabilized by carbon nanotubes (CNTs). Single-walled (pristine) and multi-walled ...

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Funzionalizzazione di single-walled nanotubi di carbonio con termo-reversibili Block Copolimeri e caratterizzazione da piccolo angolo Neutron Scattering

We demonstrate a protocol for single-walled carbon nanotube functionalization using thermo-sensitive PEO-PPO-PEO triblock copolymers in an aqueous ...

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Aliphatic ligands are typically used during the synthesis of nanoparticles to help mediate their growth in addition to operating as high-temperature ...

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Sintesi facile di micelle vermiforme dalla luce visibile mediata polimerizzazione in dispersione Utilizzando Photoredox Catalyst

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

Controlled Photoredox Ring-Opening Polymerization of O-Carboxyanhydrides Mediated by Ni/Zn Complexes

Controlled Photoredox Ring-Opening Polymerization of O-Carboxyanhydrides Mediated by Ni/Zn Complexes

Controllata di polimerizzazione per apertura di anello Photoredox di O- Carboxyanhydrides mediata da complessi di Ni/Zn

Here, we describe an effective protocol that combines photoredox Ni/Ir catalysis with the use of a Zn-alkoxide for efficient ring-opening polymerization, ...