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="Figure 1" src="/files/ftp_upload/54422/54422fig1.jpg" /> Figure 1. Schéma montrant les neuf étapes clés dans la préparation du copolymère b -PPheGE mPEG. <a href="http://ecsource.jove.com/files/ftp_upload/54422/54422fig1large.jpg" target="_blank">S&#39;il vous plaît cliquer ici pour voir une version plus grande de cette figure.</a> 1. Préparation des réactifs dans des conditions sèches <ol><li> Préparation des réactifs. <...

<ol>
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En raison de la bonne maîtrise que la polymérisation anionique fournit plus de poids moléculaire, il est l&#39;un des processus les plus appliqués dans l&#39;industrie pour la préparation de polymères à base de monomères oxirane (PEG et PPG). des conditions optimales et rigoureuses doivent être utilisées avec succès pour la polymérisation à atteindre. purification rigoureuse de tous les réactifs et appareils appropriés sont essentiels pour le caractère vivant de la synthèse. Limitations de la configurat...

En milieu aqueux, les copolymères à blocs amphiphiles se réunissent pour former des micelles de copolymères à blocs de taille nanométrique (SMCA) qui se composent d&#39;un noyau hydrophobe entouré d&#39;une enveloppe hydrophile ou couronne. Le noyau micellaire peut servir de réservoir pour l&#39;incorporation de médicaments hydrophobes; tandis que la couronne hydrophile fournit une interface entre le noyau et le milieu extérieur. Le poly (éthylène glycol) (PEG) et ses dérivés sont l&#39; une des plus importantes classes de polymères et l&#39; un des plus largement utilisés dans la formulation des médicaments. 1-3 BCMs se sont révélés être une plate - forme de délivrance de médicament digne avec plusieurs formulations reposant sur ce la technologie actuellement en développement clinique de stade tardif. 4 le plus souvent, le bloc hydrophobe du copolymère est constitué par la polycaprolactone, le poly (D, l-lactide), le poly (oxyde de propylène) ou le poly (β-benzyl-l-aspartate). 5 -9 Le groupe de Kataoka étudié micelles sphériques formés à partir de PEO b </em&gt; -PBLA Et de poly (oxyde d&#39;éthylène) - b -. (Doxorubicine conjuguée à l&#39; acide aspartique) pour la livraison de la doxorubicine (DOX) 10,11 Dans leurs rapports, ils ont mis en avant que les interactions π-tc entre le médicament conjugué à un polymère ou PBLA et sans DOX agir pour stabiliser le noyau micellaire entraînant une augmentation de la charge de médicament et de rétention. Il est établi que la compatibilité ou des interactions entre un médicament et le bloc formant noyau sont des déterminants de paramètres de performance liés à clé 12 En plus de la DOX. Un certain nombre de traitements anti - cancéreux comprennent des cycles aromatiques dans leur structure de base (par exemple, le methotrexate, olaparib, SN -38). En conséquence, il existe un intérêt considérable dans la synthèse de copolymères qui comprennent des cycles de benzyle dans les blocs formant noyau. Polymérisation par ouverture de cycle Anionique de PEG et ses dérivés permettent le contrôle de la masse moléculaire et le résultat dans les matériaux de faible polydispersité avec un bon rendement. 13,14 Ethyleoxyde de ne avec de l&#39; éther glycidylique de phényle (PheGE) ou d&#39; oxyde de styrène (SO) peut être (co) polymérisé pour former des copolymères à blocs qui forment des micelles pour la solubilisation des médicaments hydrophobes. 15-18 Le présent rapport décrit les étapes nécessaires à la polymérisation anionique vivante de phényle l&#39; éther glycidylique monomère sur le mPEG-OH en tant que macroinitiateur (figure 1). Le copolymère séquence résultant et ses agrégats sont ensuite caractérisés en termes de propriétés de la pertinence à utiliser dans l&#39;administration de médicaments.

<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

Dans cette étude, un copolymère amphiphile comprenant un bloc de formation de noyau avec des groupes phényle a été synthétisé par polymérisation anionique vivante d&#39;éther glycidylique de phényle (PheGE) le méthoxy-polyéthylène glycol (mPEG b -PPheGE). Caractérisation du copolymère a révélé une distribution moléculaire étroite (PDI &lt;1,03) et a confirmé le degré de polymérisation de mPEG 122 - b - (PheGE) 15. La concentration micellaire critique du copolymère a été évaluée en utilisant une méthode de fluorescence établie avec le comportement d&#39;agrégation évaluée par diffusion dynamique de la lumière et microscopie électronique à transmission. Le potentiel du copolymère pour une utilisation dans des applications d&#39;administration de médicaments a été évalué de façon préliminaire , y compris in vitro biocompatibilité, le chargement et la libération du médicament anticancéreux doxorubicine hydrophobe (DOX). Une formulation micellaire stable de DOX a été préparé avec des niveaux stupéfiants de chargement jusqu&#39;à 14% (% en poids), la charge de médicament efficiEncies&gt; 60% (p / p) et la libération prolongée du médicament pendant 4 jours dans des conditions physiologiquement pertinentes (pH acide et neutre, la présence d&#39;albumine). Le niveau de charge élevée de la drogue et la libération prolongée est attribuée à la stabilisation des interactions tc-π entre DOX et le bloc de formation de noyau des micelles.

<img alt="Figure 3" src="/files/ftp_upload/54422/54422fig3.jpg" /> Figure 3. Illustration de la polymérisation anionique de glycidyléther de phényle sur mPEG macroamorceur pour produire b mPEG - (PheGE) 15 pour la préparation de micelles de copolymère séquence pour un chargement de doxorubicine Le schéma illustre la déprotonation du grou...

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

Les principales étapes de polymérisation anionique vivante de l&#39; éther glycidylique de phényle (PheGE) sur méthoxy-polyéthylène glycol (mPEG b -PPheGE) sont décrits. Les micelles de copolymère séquence résultant (SMCA) ont été chargés de doxorubicine 14% (% en poids) et une libération prolongée du médicament pendant 4 jours dans des conditions physiologiquement pertinentes ont été obtenus.

Anionique Polymérisation d&#39;un copolymère amphiphile pour la préparation du copolymère bloc micelles Stabilisé par π-tc Interactions 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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Anionic Polymerization of an Amphiphilic Copolymer for Preparation of Block Copolymer Micelles Stabilized by &#960;-&#960; Stacking Interactions

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