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. Diagrama esquemático mostrando os nove passos fundamentais na preparação do copolímero b -PPheGE MPEG. <a href="http://ecsource.jove.com/files/ftp_upload/54422/54422fig1large.jpg" target="_blank">Por favor clique aqui para ver uma versão maior desta figura.</a> 1. Preparação dos reagentes sob condições secas <ol><li> Preparação dos reagentes. <ol><li> Pesa...

<ol>
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Devido a um bom controlo de polimerização aniónico que proporciona sobre o peso molecular, é um dos processos mais utilizados na indústria para a preparação de polímeros à base de monómeros oxirano (PEG e PPG). As condições óptimas e rigorosas deve ser utilizado para a polimerização com êxito para ser conseguida. purificação rigorosa de todos os reagentes e aparelhos adequados são essenciais para o personagem vivo da síntese. Limitações da configuração atual está geralmente associada à técnica...

Em meios aquosos, copolímeros em bloco anfifílicos montar para formar micelas de copolímeros de blocos de tamanho nano (SGCN) que consistem de um núcleo hidrófobo rodeado por uma camada hidrófila ou corona. O núcleo da micela pode servir como um reservatório para a incorporação de fármacos hidrófobos; enquanto, a coroa hidrofílica fornece uma interface entre o núcleo e o meio externo. Poli (etileno glicol) (PEG) e seus derivados são uma das mais importantes classes de polímeros e um dos mais amplamente utilizados na formulação de fármaco. 1-3 BCMs provaram ser uma plataforma de entrega de droga digno com várias formulações contando com este tecnologia agora em desenvolvimento clínico de fase tardia. 4 Mais vulgarmente, o bloco hidrofóbico do copolímero é constituído por poli-caprolactona, poli (D, L-lactido), poli (óxido de propileno) ou poli (β-benzil-L-aspartato). 5 -9 O grupo de Kataoka investigado micelas esféricas formadas a partir de b PEO- </em&gt; -PBLA E poli (óxido de etileno) - b -. (Doxorrubicina conjugado-ácido poliaspártico) para entrega da doxorrubicina (DOX) 10,11 Em seus relatórios, eles dizem que as interações π-¸ entre a droga polímero conjugado ou PBLA e DOX livre actuar para estabilizar o núcleo micelar resultando em aumentos da carga e retenção da droga. É estabelecido que a compatibilidade ou interações entre uma droga e o bloco formando-core são determinantes de parâmetros-chave relacionados com o desempenho 12 Além de DOX., Uma série de cancro terapêutica incluem anéis aromáticos dentro da sua estrutura de núcleo (por exemplo, metotrexato, olaparib, SN -38). Como resultado, existe um interesse significativo na síntese de copolímeros que incluem anéis de benzilo em seus blocos de formação de núcleo. Polimerização de PEG e os seus derivados aniónicos de abertura de anel permitir o controlo sobre o peso molecular e resulta em materiais de baixa polidispersão com um bom rendimento. 13,14 éthyleóxido de ne com éter fenil glicidílico (PheGE) ou óxido de estireno (SO) pode ser (co) polimerizado para formar copolímeros em bloco que formam micelas para a solubilização de fármacos hidrofóbicos. 15-18 O presente relatório descreve os passos necessários para viver polimerização aniônica de fenil glicidil monómero de éter em mPEG-OH como macroiniciador (Figura 1). O copolímero em bloco resultante e seus agregados são então caracterizados em termos de propriedades relevantes para a utilização na entrega da droga.

<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

Neste estudo, um copolímero anfifílico que inclui um bloco de formação de núcleo, com grupos fenilo foi sintetizado por polimerização aniónica vivo de éter fenil glicidílico (PheGE) em metoxi-polietileno-glicol (MPEG-b -PPheGE). Caracterização do copolímero revelou uma distribuição estreita molecular (PDI &lt;1,03) e confirmado o grau de polimerização de mPEG 122 - b - (PheGE) 15. A concentração crítica de micelas de copolimero foi avaliada usando um método de fluorescência estabelecida com o comportamento de agregação avaliada por dispersão dinâmica de luz e microscopia electrónica de transmissão. O potencial do copolímero para o uso em aplicações de distribuição de droga foi avaliada de uma forma preliminar, incluindo biocompatibilidade in vitro, o carregamento e a libertação da doxorrubicina hidrofóbico de drogas anti-cancro (DOX). Uma formulação micelar estável de DOX foi preparado com níveis de carga de fármaco até 14% (% em peso), carga de fármaco efficiacetatos&gt; 60% (w / w) e de libertação sustentada de fármaco durante 4 dias sob condições f isiologicamente relevantes (pH ácido e neutro, a presença de albumina). O nível de carga elevada de droga de libertação sustida e é atribuída a estabilizar as interacções entre π ¸-DOX e o bloco de formação de núcleo das micelas.

<img alt="Figura 3" src="/files/ftp_upload/54422/54422fig3.jpg" /> Figura 3. Ilustração da polimerização aniónica de éter de glicidilo de mPEG fenil macroiniciador para produzir MPEG-b - (PheGE) 15 para a preparação de micelas de copolímero em bloco para o carregamento de doxorrubicina O esquema ilustra a desprotonação do grupo hidroxilo de mPEG utilizando naftaleno de potáss...

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

Os principais passos da vida polimerização aniônica de éter fenil glicidílico (PheGE) sobre metoxi-polietileno glicol (MPEG-b -PPheGE) são descritos. As micelas de copolímero em bloco resultante (SGCN) foram carregados com doxorrubicina 14% (% em peso) e de libertação sustentada de fármaco durante 4 dias sob condições f isiologicamente relevantes foi obtido.

Aniônico polimerização de um copolímero anfifílicas para Preparação de copolímero em bloco As micelas estabilizada por interacções de empilhamento π-¸

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

Synthetic Polymers

Ethers, Epoxides, Sulfides

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