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. Skematisk viser de ni vigtigste skridt i forberedelsen af mPEG B -PPheGE copolymer. <a href="http://ecsource.jove.com/files/ftp_upload/54422/54422fig1large.jpg" target="_blank">Klik her for at se en større version af dette tal.</a> 1. Forberedelse af reagenser under tørre forhold <ol><li> Fremstilling af reagenserne. <ol><li> Afvej 15 g mPEG-5K (M n = 5.40...

<ol>
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På grund af den gode kontrol, anionisk polymerisation giver over molekylvægten er det en af ​​de mest anvendte processer i industrien til fremstilling af polymerer baseret på oxiran monomerer (PEG og PPG). Optimale og stringente betingelser skal anvendes for vellykket polymerisation skal opnås. Streng oprensning af alle reagenser og passende apparat er essentielle for levende karakter af syntesen. Begrænsninger i den nuværende setup er for det meste forbundet med overførslen teknik, der er afhængig af kanyle...

I vandige medier, amfifile blokcopolymerer samles for at danne nanostørrelse blokcopolymer miceller (BCMS), der består af en hydrofob kerne omgivet af en hydrofil skal eller corona. Den micelle kerne kan tjene som et reservoir for inkorporering af hydrofobe stoffer; mens den hydrofile corona giver en grænseflade mellem kernen og det ydre medium. Poly (ethylenglycol) (PEG) og derivater deraf er en af de vigtigste klasser af polymerer og en af de mest udbredte i lægemiddelformulering. 1-3 BCMS har vist sig at være en værdig drug delivery platform med flere formuleringer afhængige af dette teknologi nu i sen klinisk udvikling. 4 Mest almindeligt, den hydrofobe blok af copolymeren består af polycaprolacton, poly (D, L-lactid), poly (propylenoxid) eller poly (β-benzyl-L-aspartat). 5 -9 Kataoka gruppe undersøgte sfæriske miceller dannet af PEO- b </em&gt; -PBLA Og poly (ethylenoxid) - b -. (Polyasparaginsyre-konjugeret doxorubicin) til levering af doxorubicin (DOX) 10,11 i deres rapporter, de fremførte, at π-Tr interaktioner mellem polymer-konjugeret lægemiddel eller PBLA og gratis DOX handle for at stabilisere micelle kerne resulterer i stigninger i medikamentifyldning og fastholdelse. Det er fastslået, at kompatibilitet eller interaktioner mellem et lægemiddel og kernen-dannende blok er determinanter for key performance parametre. 12 Ud over DOX, en række kræftmedicin omfatter aromatiske ringe inden for deres kerne struktur (fx methotrexat, olaparib, SN -38). Som følge heraf er der betydelig interesse i syntesen af ​​copolymerer, der omfatter benzyl ringe i deres kernedannende blokke. Anionisk ringåbnende polymerisation af PEG og dets derivater muliggøre kontrol over molekylvægten og resulterer i materialer med lav polydispersitet i godt udbytte. 13,14 Ethylene oxid med phenylglycidylether (PheGE) eller styren oxid (SO) kan være (co) polymeriseres til at danne blokcopolymerer, der danner miceller til solubilisering af hydrofobe stoffer. 15-18 Den aktuelle rapport beskriver de nødvendige skridt for at leve anioniske polymerisering af phenyl glycidylether monomer på mPEG-OH som makroinitiator (figur 1). Den resulterende blokcopolymer og dets aggregater derpå karakteriseret i form af egenskaberne relevante at bruge i lægemiddeladministration.

<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 denne undersøgelse blev en amfifil copolymer, der indbefatter en kerne-dannende blok med phenylgrupper syntetiseret ved levende anionisk polymerisation af phenyl glycidylether (PheGE) på methoxy-polyethylenglycol (mPEG B -PPheGE). Karakterisering af copolymeren afslørede en smal molekylær fordeling (PDI &lt;1,03) og bekræftede polymerisationsgrad mPEG 122 - b - (PheGE) 15. Den kritiske micellekoncentration af copolymeren blev vurderet ved anvendelse af en etableret fluorescensmetode med aggregeringen adfærd vurderes ved dynamisk lysspredning og transmission elektronisk mikroskopi. Potentialet af copolymeren til brug i lægemiddeltilførselsanvendelser blev evalueret i en foreløbig måde, herunder in vitro biokompatibilitet, lastning og frigivelse af den hydrofobe anti-cancer stof doxorubicin (DOX). En stabil micelle formulering af DOX blev fremstillet med medikamentloading niveauer op til 14% (vægt-%), lægemiddelfyldning efficiencies&gt; 60% (vægt / vægt) og vedvarende afgivelse af lægemidlet over 4 dage under fysiologisk relevante betingelser (surt og neutralt pH, tilstedeværelse af albumin). Det høje medikamentbelastning niveau og langvarig frigivelse tilskrives stabilisere n-π interaktioner mellem DOX og kernedannende blok af micellerne.

<img alt="Figur 3" src="/files/ftp_upload/54422/54422fig3.jpg" /> Figur 3. Illustration af den anioniske polymerisation af phenylglycidylether på mPEG makroinitiator til frembringelse mPEG b - (PheGE) 15 til fremstilling af blokcopolymer-miceller til lastning af doxorubicin Den skematiske illustrerer deprotonering af hydroxylgruppen i mPEG hjælp naphthalen kalium. som en radik...

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 vigtigste trin i levende anioniske polymerisering af phenylglycidylether (PheGE) på methoxy-polyethylenglycol (mPEG b -PPheGE) er beskrevet. De resulterende blokcopolymer miceller (BCMS) blev fyldt med doxorubicin 14% (vægt%) og vedvarende afgivelse af lægemidlet over 4 dage under fysiologisk relevante betingelser blev opnået.

Anionisk polymerisation af en amfifil Copolymer for Udarbejdelse af blokcopolymer Miceller stabiliseret af π-Tr Stacking 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

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