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="Figur 1" src="/files/ftp_upload/54422/54422fig1.jpg" /> Figur 1. Schematisk visar de nio viktiga steg i beredningen av MPEG b -PPheGE sampolymer. <a href="http://ecsource.jove.com/files/ftp_upload/54422/54422fig1large.jpg" target="_blank">Klicka här för att se en större version av denna siffra.</a> 1. Beredning av reagenser på torr vägbana <ol><li> Framställning av reagensen. <ol><li> Väg 15 g av mPEG-5K (Mn = 5400...

<ol>
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På grund av den goda kontroll som anjonpolymerisation ger över molekylvikt är en av de mest tillämpade processer i industrin för framställning av polymerer baserade på oxiran-monomerer (PEG och PPG). Optimala och stringenta betingelser måste användas för framgångsrik polymerisation skall uppnås. Rigorös rening av alla reagenser och lämpliga apparater är väsentliga för den levande karaktären av syntesen. Begränsningar i det nuvarande uppställnings är oftast i samband med överföringsteknik som bygge...

I vattenhaltiga medier, amfifila segmentsampolymerer samlas för att bilda nanostora segmentsampolymer miceller (BCMS) som består av en hydrofob kärna omgiven av ett hydrofilt skal eller korona. Micellen kärna kan tjäna som en reservoar för inkorporering av hydrofoba läkemedel; medan, tillhandahåller den hydrofila korona ett gränssnitt mellan kärnan och det externa mediet. Poly (etylenglykol) (PEG) och dess derivat är en av de viktigaste klasserna av polymerer och en av de mest använda inom läkemedelsformulering. 1-3 BCMS har visat sig vara en värdig läkemedelsavgivning plattform med flera formuleringar förlita sig på denna teknik nu i sen klinisk utvecklingsfas. 4 vanligast är det hydrofoba blocket av sampolymeren består av polykaprolakton, poly (D, L-laktid), poly (propylenoxid) eller poly (β-bensyl-L-aspartat). 5 -9 Kataoka grupp undersökte sfäriska miceller bildade från PEO- B </em&gt; -PBLA Och poly (etylenoxid) - b -. (Polyasparaginsyra-konjugerat doxorubicin) för leverans av doxorubicin (DOX) 10,11 i sina rapporter, de sätter fram att π-Tt interaktioner mellan polymer-konjugerat läkemedel eller PBLA och fri DOX agera för att stabilisera micellen kärnan resulterar i ökade läkemedelsladdning och lagring. Det är klarlagt att kompatibiliteten eller interaktioner mellan läkemedel och kärnbildande blocket är faktorer som påverkar viktiga prestandarelaterade parametrar. 12 Förutom DOX, ett antal cancerterapi inkluderar aromatiska ringar inom sin kärnstruktur (t.ex. metotrexat, olaparib, SN -38). Som ett resultat finns det ett stort intresse för syntes av sampolymerer som innefattar bensyl ringar i sina kärnbildande block. Anjonisk ringöppningspolymerisation av PEG och dess derivat möjliggöra kontroll över molekylvikt och resulterar i material med låg polydispersitet i gott utbyte. 13,14 etylenne oxid med fenylglycidyleter (PheGE) eller styrenoxid (SO) kan vara (sam) polymeriseras för att bilda segmentsampolymerer som bildar miceller för solubilisering av hydrofoba läkemedel. 15-18 Den aktuella rapporten beskrivs de åtgärder som krävs för att leva anjoniska polymerisationen av fenyl glycidyleter monomer på mPEG-OH som makroinitiator (Figur 1). Den resulterande segmentsampolymeren och dess aggregat karakteriseras sedan med avseende på egenskaper som är relevanta för användning i läkemedelsavgivning.

<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

I denna studie var en amfifil sampolymer som innehåller en kämbildande block med fenylgrupper syntetiseras genom levande anjonisk polymerisation av fenylglycidyleter (PheGE) på metoxi-polyetylenglykol (MPEG-b -PPheGE). Karakterisering av sampolymeren visade en snäv molekylfördelning (PDI &lt;1,03) och som bekräftas av graden av polymerisation av mPEG 122 - b - (PheGE) 15. Den kritiska micellkoncentrationen av sampolymeren utvärderades med användning av en etablerad fluorescensmetod med aggregationen beteende utvärderades genom dynamisk ljusspridning och transmission elektronmikroskopi. Potentialen av sampolymeren för användning i läkemedelsleveranstillämpningar utvärderades i en preliminär sätt, inklusive in vitro biokompatibilitet, lastning och frigörande av hydrofoba läkemedel mot cancer doxorubicin (DOX). En stabil micell formulering av DOX framställdes med läkemedelsbelastningsnivåer upp till 14% (vikt%), läkemedelsbelastning effici-film&gt; 60% (vikt / vikt) och utdragen frisättning av läkemedel under 4 dygn under fysiologiskt relevanta förhållanden (surt och neutralt pH, närvaro av albumin). Den höga läkemedelsladdningsnivån och fördröjd frisättning tillskrivs att stabilisera n-π växelverkan mellan DOX och kärnbildande block av micellerna.

<img alt="Figur 3" src="/files/ftp_upload/54422/54422fig3.jpg" /> Figur 3. Illustration av den anjoniska polymerisationen av fenylglycidyleter på mPEG makroinitiator för att producera MPEG b - (PheGE) 15 för framställning av segmentsampolymer miceller för laddning av doxorubicin Den schematiska illustrerar deprotonering av hydroxylgruppen hos mPEG med användning av naftalen kalium....

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

De viktigaste stegen av levande anjoniska polymerisationen av fenylglycidyleter (PheGE) på metoxi-polyetylenglykol (MPEG b -PPheGE) beskrivs. De resulterande segmentsampolymer miceller (BCMS) laddades med doxorubicin 14% (vikt-%) och utdragen frisättning av läkemedel under 4 dygn under fysiologiskt relevanta förhållanden erhölls.

Anjoniska polymerisationen av en amfifila sampolymeren för framställning av segmentsampolymeren Miceller stabiliseras genom π-Tt stapling interaktioner

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

SCIENTISTS IN ACTION

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