This study was supported by the grant from AACP New Pharmacy Faculty Research Award Program, Medical Research Foundation of Oregon New Investigator Grant, Oregon State University-Startup fund, and Pacific University, School of Pharmacy Start-up fund.

ソルベントキャスト法により個人およびマルチ薬剤ロードミセルの調製<ol><li>デュアル薬物ミセルのために各1mg（DDM）でDTX 1 mgまたはそれEVR 1ミリグラムまたは両方の薬剤を秤量。 </li><li> PEG 2000の15 mgの秤量- -pla 1800またはPEG 4000 bを - B -pla 2200個人またはDDMのいずれかのために。 </li><li>薬物/薬物や5ミリリットルの丸底フラスコ中のアセトニトリルと場所の0.5ミリリットル中にポリマーを溶解します。 </li><li>ロータリーエバポレーターを用いて減圧下薬（S） - ポリマーアセトニトリル溶液を蒸発させて、薄い薬物分散ポリマーフィルムを形成します。 100rpmで、40°Cのウォーターバスの温度とさらに3分間100ミリバールに還元し、5分間260ミリバールの真空圧力に回転蒸発器を設定します。 </li><li> 50 O℃で脱イオン水0.5mlを有する薬物-ポリマーフィルムを再水和及び穏やかにミセルを形成するために、フラスコを振盪します。 </li><li>結果をフィルター1.5ミリリットル遠心管に任意の未溶解した薬物または汚染物質を除去するために0.2μmのナイロンフィルターを通してミセル溶液をる。 </li></ol>逆相高速液体クロマトグラフィー（RP-HPLC）を用いてミセル中の薬物負荷と安定性の評価2。 <ol><li> 1ml /分の流速で0.1％のリン酸および1％のメタノールを含有するアセトニトリル/水の移動相（62/38）を用いてアイソクラチックモードで、40℃で平衡化C8カラムでRP-HPLC分析を行い、 10μlの注入量。 </li><li>初期薬物負荷を決定するために、RP-HPLCで分析する前に、移動相中の100：新たに調製したミセル（セクション1）1を希釈します。 RP-HPLCにより再評価し、24時間かけてミセル中の薬剤（複数可）の安定性を決定するために、移動相に100希釈したサンプル：ストア希釈していない個々のミセルと48時間室温（25 O℃）でのDDMとは、新鮮な1を準備します。 </li><li>それぞれ227および279 nmでのDTXとEVRピークを監視1.7および5.7分の保持時間で、それぞれ。三連ですべての測定を実行します。平均±SD薬物負荷として存在するデータ。 </li></ol>動的光散乱によってミセル粒子サイズの3アセスメント（DLS） <ol><li> 1.5 mg / mlの最終的なポリマー濃度を得るために、1：20の比率で脱イオン水（セクション1に記載したように）新たに調製されたミセルを希釈します。 </li><li>散乱を決定するために、173℃でHe-Neレーザー（633nm）の強度を測定します。 2分間プレ平衡化した後、25℃ですべての測定を実行します。 </li><li>三連ですべての測定を実行します。分布の多分散指数（PDI）と共に、平均値±SD Z平均サイズとして存在するデータ。 </li></ol>個々のミセルとDDMから4次評価でのインビトロ薬物放出<ol><li>ミセルの1ロード2.5ミリリットルがで3ミリリットル透析カセットにセクションで説明したように、個々のミセルとDDMを準備7,000グラム/モルの分子量カットオフ（MWCO）。 注：このMWCOは、カセットの外に自由に拡散することにより、シンク条件を確保するために関連付けられていないポリマー分子と一緒に遊離薬物（複数可）を有効にするために選ばれました。 </li><li> （株式200 mM溶液を希釈することにより調製）10mMのpH7.4のリン酸緩衝液2.5リットルにカセットを置き、シンク条件を確保するために、バッファごとに3時間を変更します。実験期間を通じて37°Cの時のバッファの温度を維持します。 </li><li> 0、0.5、1、2、3、6、9、12、24、および48時間では、カセット内の溶液の150μLを撤回し、新鮮な緩衝液150μlで交換してください。 </li><li>セクション2で確立された薬物の濃度を決定するためにRP-HPLCを用いてサンプルを分析します。薬剤（複数可）stastiticalソフトウェアを使用して、1つの位相指数関数的会合を持つ単純な拡散モデルに基づく放出データを曲線適合。 </li><li> Eの薬物放出（T 1/2）の50％に達するのに必要な時間を算出しますフィッティング曲線に基づいて、個々のミセルまたはDDMでACH薬。四つですべての測定を実行します。 </li></ol>

<ol>
	<li>Yokoyama, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polymeric+micelles+as+a+new+drug+carrier+system+and+their+required+considerations+for+clinical+trials.">Polymeric micelles as a new drug carrier system and their required considerations for clinical trials.</a> Expert Opin Drug Deliv. 7, 145-158 (2010).</li><li>Shin, H. C., Alani, A. W., Rao, D. A., Rockich, N. C., Kwon, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multi-drug+loaded+polymeric+micelles+for+simultaneous+delivery+of+poorly+soluble+anticancer+drugs.">Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs.</a> J Control Release. 140, 294-300 (2009).</li><li>Adams, M. L., Lavasanifar, A., Kwon, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amphiphilic+block+copolymers+for+drug+delivery.">Amphiphilic block copolymers for drug delivery.</a> J Pharm Sci. 92, 1343-1355 (2003).</li><li>Oerlemans, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polymeric+micelles+in+anticancer+therapy:+targeting,+imaging+and+triggered+release.">Polymeric micelles in anticancer therapy: targeting, imaging and triggered release.</a> Pharm Res. 27, 2569-2589 (2010).</li><li>Shin, H. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+3-in-1+polymeric+micelle+nanocontainer+for+poorly+water-soluble+drugs.">A 3-in-1 polymeric micelle nanocontainer for poorly water-soluble drugs.</a> Mol Pharm. 8, 1257-1265 (2011).</li><li>Hasenstein, J. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antitumor+activity+of+Triolimus:+a+novel+multidrug-loaded+micelle+containing+Paclitaxel+Rapamycin,+and+17-AAG.">Antitumor activity of Triolimus: a novel multidrug-loaded micelle containing Paclitaxel Rapamycin, and 17-AAG.</a> Mol Cancer Ther. 11, 2233-2242 (2012).</li><li>Mazzaferro, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bivalent+sequential+binding+of+docetaxel+to+methyl-beta-cyclodextrin.">Bivalent sequential binding of docetaxel to methyl-beta-cyclodextrin.</a> Int J Pharm. 416, 171-180 (2011).</li><li>Iwase, Y., Maitani, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Preparation+and+in+vivo+evaluation+of+liposomal+everolimus+for+lung+carcinoma+and+thyroid+carcinoma.">Preparation and in vivo evaluation of liposomal everolimus for lung carcinoma and thyroid carcinoma.</a> Biol Pharm Bull. 35, 975-979 (2012).</li><li>Mishra, G. P., Doddapaneni, B. S., Nguyen, D., Alani, A. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antiangiogenic+effect+of+docetaxel+and+everolimus+as+individual+and+dual-drug-loaded+micellar+nanocarriers.">Antiangiogenic effect of docetaxel and everolimus as individual and dual-drug-loaded micellar nanocarriers.</a> Pharm Res. 31, 660-669 (2014).</li><li>Xu, W., Ling, P., Zhang, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Polymeric+micelles,+a+promising+drug+delivery+system+to+enhance+bioavailability+of+poorly+water-soluble+drugs.">Polymeric micelles, a promising drug delivery system to enhance bioavailability of poorly water-soluble drugs.</a> J Drug Deliv. 2013, 340315 (2013).</li><li>Lavasanifar, A., Samuel, J., Kwon, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Poly(ethylene+oxide)-block-poly(L-amino+acid)+micelles+for+drug+delivery.">Poly(ethylene oxide)-block-poly(L-amino acid) micelles for drug delivery.</a> Adv Drug Deliv Rev. 54, 169-190 (2002).</li></ol>

The authors have nothing to disclose.

The use of polymeric micelles for drug delivery continues to expand due to their versatility and ability to deliver hydrophobic drugs for various disease states. Therefore, the techniques needed to prepare and characterize these formulations prior to use in cell culture or animals is a critical first step to determine the best pairing between the drug and the polymer. PEG-b-PLA are excellent amphiphilic block copolymers for drug delivery purposes. However, the block length of the hydrophilic and hydrophobic s...

親水性および疎水性ドメインからなる繰り返し構造を有する両親媒性ブロック共重合体は自発的に重合体ミセルとして知られている三次元の高分子集合体を形成するために自己組織化することができます。これらの構造は、親水性シェルによって囲まれた内側の疎水性コアを有します。疎水性コアは、ポリマー骨格上に疎水性相互作用を介して、または化学結合により物理的捕捉のいずれかによって疎水性薬物を組み込む能力を有している。1、多くの利点は、薬物送達のためのミセルを形成するために、これらのブロックコポリマーを使用して存在します。これらは難溶性薬物、組み込まれた薬物の薬物動態を改善し、生体適合性および/ ​​またはポリマーの生分解性の組み込みは、従来の可溶化剤への安全な代替なり含む2高分子ミセルを使用する別の利点は、15-間に、それらのコロイド粒子のサイズであります150nmの3、PAのためにそれらが魅力的renteral配信。このため、過去20年間にポリマーミセルは、特に、癌治療のための難水溶性薬物のための実行可能な薬物送達システムとして浮上している。3,4 現在臨床試験を受けている癌治療のための5つの高分子ミセル製剤がある。最後にポリエチレンオキシドを含むトリブロック共重合体であるが、臨床試験中でミセルの4つは、PEGベースのジブロックコポリマーです。これらのミセルのサイズは、85ナノメートル、20ナノメートルから変化しました。 PEGベースのポリマーを使用することの利点は、その生体適合性であり、第二のブロックに応じて、また生分解性であることができます。 polyethyleneglycol- ブロック -polylactic酸（-pla PEG- B）高分子ミセルに基づいて、最近、新しい薬物送達システムは、複数の抗癌剤の同時送達のために開発されています。 PEG-B-PLAミセルは、生体適合性および生分解性の両方です。ロードされたミセルのように示されているこれらの多剤ynergistic インビトロおよびインビボ 2,5,6- における異なる癌モデルの阻害および抵抗を防止するために化学療法で複数の薬物を利用し、毒性を低下させる現在のパラダイムに適合。したがって、癌および他の疾患状態において使用するためのこれらのミセルの薬物送達システムを調製し、特徴付けるにおける大きな関心があります。 私たち以下の作業では、このようなミセルが関心の疾患状態でそれらを評価する前に準備し、特徴付けすることが可能なステップバイステップのプロセスを概説しています。この研究の目的のために2難溶性の抗がん剤は、ドセタキセル（DTX）及びエベロリムス（EVR）が選択されています。 DTXとEVRの両方がそれぞれML / 1.9と9.6μgのに固有の水溶解性と難水溶性化合物である。分子量の異なる7,8-二PEG-Bの -plaポリマーを配合、ポリマーのためのビルディングブロックとして、このプロトコルで使用されていましたミセル、-pla 1800（3800ダ）およびPEG 4000 B - - -pla 2200（6200 Da）でBこれらのポリマーは、PEG 2000です。 PEG-Bの -plaミセルは、したがって、個別に組み合わせてDTXとEVRのためのナノキャリアとしてのユニークなプラットフォームを提供することができます。必要な試薬/材料および装置は、これらのミセルを準備し、特徴づけるために必要な、表1に記載されています。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>PEG2000-b-PLA1800</td>
			<td>Advanced Polymer Materials, Inc</td>
			<td>6-01- PLA/2000</td>
			<td>PLA MW can be specified on ordering</td>
		</tr>
		<tr>
			<td>PEG4000-b-PLA2200</td>
			<td>Advanced Polymer Materials, Inc</td>
			<td>6-01- PLA/4000</td>
			<td>PLA MW can be specified on ordering</td>
		</tr>
		<tr>
			<td>Docetaxel</td>
			<td>LC Laboratories</td>
			<td>D-1000</td>
			<td>100 mg</td>
		</tr>
		<tr>
			<td>Everolimus</td>
			<td>LC Laboratories</td>
			<td>E-4040</td>
			<td>100 mg</td>
		</tr>
		<tr>
			<td>Acetonitrile</td>
			<td>EMD/VWR</td>
			<td>EM-AX0145-1</td>
			<td>HPLC grade; 4 L</td>
		</tr>
		<tr>
			<td>Round bottom flask&#160;</td>
			<td>Glassco/VWR</td>
			<td>89426-496</td>
			<td>5 mL</td>
		</tr>
		<tr>
			<td>RV 10 Control Rotary Evaporators</td>
			<td>IKA Works</td>
			<td>8025001</td>
			<td>Rotoevaporator</td>
		</tr>
		<tr>
			<td>Shimadzhu HPLC with DAD detector</td>
			<td>Shimadzhu</td>
			<td></td>
			<td>RP-HPLC</td>
		</tr>
		<tr>
			<td>Slide-a-lyzer dialysis casette MWCO 7000</td>
			<td>Thermo Scientific, Inc</td>
			<td>66370</td>
			<td>3 mL</td>
		</tr>
		<tr>
			<td>Phosphate buffer pH 7.4 200 mM</td>
			<td>VWR</td>
			<td>100190-870</td>
			<td>500 mL</td>
		</tr>
		<tr>
			<td>Malvern NanoZS</td>
			<td>Malvern Instruments, UK</td>
			<td></td>
			<td>DLS</td>
		</tr>
		<tr>
			<td>Nylon filter</td>
			<td>Acrodisc/VWR</td>
			<td>28143-242</td>
			<td>13 mm; 0.2&#181;M</td>
		</tr>
		<tr>
			<td>Phosphoric acid, NF</td>
			<td>Spectrum Chemical/VWR</td>
			<td>700000-626</td>
			<td>100 mL</td>
		</tr>
		<tr>
			<td>GraphPad Prism</td>
			<td><a href="http://www.graphpad.com/">www.graphpad.com</a></td>
			<td></td>
			<td>Analysis software</td>
		</tr>
		<tr>
			<td>Zorbax SB-C8 Rapid Resolution cartridge&#160;</td>
			<td>Agilent Technologies</td>
			<td>866953-906</td>
			<td>4.6 &#215;75mm, 3.5 micron</td>
		</tr>
	</tbody>
</table>

preparation and characterization of individual and multi-drug loaded physically entrapped polymeric micelles

polyethyleneglycol- ブロック -polylactic酸（PEG-B-PLA）のような両親媒性ブロックコポリマーは、水性環境中の親水性シェルによって囲まれた疎水性コアを形成し、その臨界ミセル濃度以上のミセルに自己組織化することができます。これらのミセルのコアは、ドセタキセル（DTX）とエベロリムス（EVR）のような疎水性、水難溶性薬物をロードするために利用することができます。ミセル構造と薬物負荷能力の体系的特徴付けを行うことができ、 インビトロおよびインビボ研究の前に重要です。本明細書に記載されたプロトコルの目的は、標準化されたミセル生成物を達成するの​​に必要な特性評価手順を提供することにあります。 DTXとEVRはそれぞれ、これらのミセルの調製は、それぞれ、1.86および1.85 mg / mlの、にDTXとEVRの水溶性を増加させ、溶媒キャスティングを介して達成することができるML / 1.9と9.6μgの固有の溶解度を有します。 evalのミセル中の薬物安定性48時間にわたって室温でuatedは、薬物の97％以上が溶液中に保持されていることを示しています。ミセルのサイズは、動的光散乱法を用いて評価し、これらのミセルの大きさが50nm未満であったポリマーの分子量に依存することが示されました。ミセルからの薬物放出は、48時間にわたって37℃でO pH7.4のシンク条件下で透析を用いて評価しました。カーブフィッティングの結果は、薬物の放出は、それが拡散が駆動されることを示す一次プロセスによって駆動されることを示します。

個々のDTXまたはEVRミセルおよびミセルが正常にPEG 4000のいずれかで処方される-pla bは PEG-でDTXとEVR DDM - B -pla 2200またはPEG 2000 - B -pla 1800（ 図1）。 48時間（ 図2）を介して-pla 1800 bは - -pla 2200またはPEG 2000 B - DTX、EVR、とDDMは、PEG 4000で同様の安定性を?...

Watch this Scientific Journal Video about Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles at JoVE.com

Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles

The goal of this protocol is to describe the preparation and characterization of physically entrapped, poorly water soluble drugs in micellar drug delivery systems composed of amphiphilic block copolymers.

調製とキャラクタリゼーション個々のとマルチ薬ロード物理的に捕捉さ高分子ミセル

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

preparation-characterization-individual-multi-drug-loaded-physically

Research

JoVE Journal

Chemistry

11.2K ビュー.  Pacific University. The goal of this protocol is to describe the preparation and characterization of physically entrapped, poorly water soluble drugs in micellar drug delivery systems composed of amphiphilic block copolymers.

ビデオ: Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid phase by using combinatorial chemistry. One of the most well studied classes of peptidomimetics is peptoids. Peptoids are easy to synthesize and have been shown to be proteolysis-resistant and cell-permeable. Over the past decade, many useful protein ligands have been identified through screening of peptoid libraries. However, most of the ligands identified from peptoid libraries do not display high affinity, with rare exceptions. This may be due, in part, to the lack of chiral centers and conformational constraints in peptoid molecules. Recently, we described a new synthetic route to access peptide tertiary amides (PTAs). PTAs are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. With side chains on both &#945;-carbon and main chain nitrogen atoms, the conformation of these molecules are greatly constrained by sterical hindrance and allylic 1,3 strain. (Figure 1) Our study suggests that these PTA molecules are highly structured in solution and can be used to identify protein ligands. We believe that these molecules can be a future source of high-affinity protein ligands. Here we describe the synthetic method combining the power of both split-and-pool and sub-monomer strategies to synthesize a sample one-bead one-compound (OBOC) library of PTAs.

Peptide tertiary amides (PTAs) are a superfamily of peptidomimetics that include but are not limited to peptides, peptoids and N-methylated peptides. Here we describe a synthetic method which combines&#160;both split-and-pool and sub-monomer strategies to synthesize a one-bead one-compound library of PTAs.

ペプチド第三級アミドライブラリのスプリット·アンド·プールの合成とキャラクタリゼーション

Peptidomimetics are great sources of protein ligands. The oligomeric nature of these compounds enables us to access large synthetic libraries on solid ...

化学

Synthesis and Characterization of Functionalized Metal-organic Frameworks

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and technological applications. Their signature property is their ultrahigh porosity, which however imparts a series of challenges when it comes to both constructing them and working with them. Securing desired MOF chemical and physical functionality by linker/node assembly into a highly porous framework of choice can pose difficulties, as less porous and more thermodynamically stable congeners (e.g., other crystalline polymorphs, catenated analogues) are often preferentially obtained by conventional synthesis methods. Once the desired product is obtained, its characterization often requires specialized techniques that address complications potentially arising from, for example, guest-molecule loss or preferential orientation of microcrystallites. Finally, accessing the large voids inside the MOFs for use in applications that involve gases can be problematic, as frameworks may be subject to collapse during removal of solvent molecules (remnants of solvothermal synthesis). In this paper, we describe synthesis and characterization methods routinely utilized in our lab either to solve or circumvent these issues. The methods include solvent-assisted linker exchange, powder X-ray diffraction in capillaries, and materials activation (cavity evacuation) by supercritical CO2 drying. Finally, we provide a protocol for determining a suitable pressure region for applying the Brunauer-Emmett-Teller analysis to nitrogen isotherms, so as to estimate surface area of MOFs with good accuracy.

Synthesis, activation, and characterization of intentionally designed metal-organic framework materials is challenging, especially when building blocks are incompatible or unwanted polymorphs are thermodynamically favored over desired forms. We describe how applications of solvent-assisted linker exchange, powder X-ray diffraction in capillaries and activation via supercritical CO2 drying, can address some of these challenges.

官能化有機金属構造体の合成とキャラクタリゼーション

Metal-organic frameworks have attracted extraordinary amounts of research attention, as they are attractive candidates for numerous industrial and ...

Preparation and Characterization of SDF-1&#945;-Chitosan-Dextran Sulfate Nanoparticles

Chitosan (CS) and dextran sulfate (DS) are charged polysaccharides (glycans), which form polyelectrolyte complex-based nanoparticles when mixed under appropriate conditions. The glycan nanoparticles are useful carriers for protein factors, which facilitate the in vivo delivery of the proteins and sustain their retention in the targeted tissue. The glycan polyelectrolyte complexes are also ideal for protein delivery, as the incorporation is carried out in aqueous solution, which reduces the likelihood of inactivation of the proteins. Proteins with a heparin-binding site adhere to dextran sulfate readily, and are, in turn, stabilized by the binding. These particles are also less inflammatory and toxic when delivered in vivo. In the protocol described below, SDF-1&#945; (Stromal cell-derived factor-1&#945;), a stem cell homing factor, is first mixed and incubated with dextran sulfate. Chitosan is added to the mixture to form polyelectrolyte complexes, followed by zinc sulfate to stabilize the complexes with zinc bridges. The resultant SDF-1&#945;-DS-CS particles are measured for size (diameter) and surface charge (zeta potential). The amount of the incorporated SDF-1&#945; is determined, followed by measurements of its in vitro release rate and its chemotactic activity in a particle-bound form.

Preparation and Characterization of SDF-1&amp;#945;-Chitosan-Dextran Sulfate Nanoparticles

The objective of this protocol is to incorporate SDF-1&#945;, a stem cell homing factor, into dextran sulfate-chitosan nanoparticles. The resultant particles are measured for their size and zeta potential, as well as the content, activity, and in vitro release rate of SDF-1&#945; from the nanoparticles.

SDF-1α-キトサン硫酸デキストランナノ粒子の調製とキャラクタリゼーション

Chitosan (CS) and dextran sulfate (DS) are charged polysaccharides (glycans), which form polyelectrolyte complex-based nanoparticles when mixed under ...

Synthesis and Characterization of Supramolecular Colloids

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical properties for applications in photonics, drug delivery and coating technology. Here we present a new family of colloidal building blocks, coined supramolecular colloids, whose self-assembly is controlled through surface-functionalization with a benzene-1,3,5-tricarboxamide (BTA) derived supramolecular moiety. Such BTAs interact via directional, strong, yet reversible hydrogen-bonds with other identical BTAs. Herein, a protocol is presented that describes how to couple these BTAs to colloids and how to quantify the number of coupling sites, which determines the multivalency of the supramolecular colloids. Light scattering measurements show that the refractive index of the colloids is almost matched with that of the solvent, which strongly reduces the van der Waals forces between the colloids. Before photo-activation, the colloids remain well dispersed, as the BTAs are equipped with a photo-labile group that blocks the formation of hydrogen-bonds. Controlled deprotection with UV-light activates the short-range hydrogen-bonds between the BTAs, which triggers the colloidal self-assembly. The evolution from the dispersed state to the clustered state is monitored by confocal microscopy. These results are further quantified by image analysis with simple routines using ImageJ and Matlab. This merger of supramolecular chemistry and colloidal science offers a direct route towards light- and thermo-responsive colloidal assembly encoded in the surface-grafted monolayer.

A protocol for the synthesis and characterization of colloids coated with supramolecular moieties is described. These supramolecular colloids undergo self-assembly upon the activation of the hydrogen-bonds between the surface-anchored molecules by UV-light.

超分子コロイドの合成とキャラクタリゼーション

Control over colloidal assembly is of utmost importance for the development of functional colloidal materials with tailored structural and mechanical ...

Low-energy Cathodoluminescence for (Oxy)Nitride Phosphors

Nitride and oxynitride (Sialon) phosphors are good candidates for the ultraviolet and visible emission applications. High performance, good stability and flexibility of their emission properties can be achieved by controlling their composition and dopants. However, a lot of work is still required to improve their properties and to reduce the production cost. A possible approach is to correlate the luminescence properties of the Sialon particles with their local structural and chemical environment in order to optimize their growth parameters and find novel phosphors. For such a purpose, the low-voltage cathodoluminescence (CL) microscopy is a powerful technique. The use of electron as an excitation source allows detecting most of the luminescence centers, revealing their luminescence distribution spatially and in depth, directly comparing CL results with the other electron-based techniques, and investigating the stability of their luminescence properties under stress. Such advantages for phosphors characterization will be highlighted through examples of investigation on several Sialon phosphors by low-energy CL.

Low-energy Cathodoluminescence for OxyNitride Phosphors

An excellent chemical and luminescence stabilities of (oxy)nitride phosphors present it as an promising alternative to currently used sulfide and oxide phosphors. In this paper, we present the way to investigate its local luminescence properties using low-energy cathodoluminescence (CL).

（オキシ）窒化物蛍光体のための低エネルギーのカソードルミネッセンス

Nitride and oxynitride (Sialon) phosphors are good candidates for the ultraviolet and visible emission applications. High performance, good stability and ...

Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst

Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins with the synthesis of a hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) homopolymer using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Under mild visible light irradiation (&#955; = 460 nm, 0.7 mW/cm2), this macro-chain transfer agent (macro-CTA) in the presence of a ruthenium based photoredox catalyst, Ru(bpy)3Cl2 can be chain extended with a second monomer to form a well-defined block copolymer in a process known as Photoinduced Electron Transfer RAFT (PET-RAFT). When PET-RAFT is used to chain extend POEGMA with benzyl methacrylate (BzMA) in ethanol (EtOH), polymeric nanoparticles with different morphologies are formed in situ according to a polymerization-induced self-assembly (PISA) mechanism. Self-assembly into nanoparticles presenting POEGMA chains at the corona and poly(benzyl methacrylate) (PBzMA) chains in the core occurs in situ due to the growing insolubility of the PBzMA block in ethanol. Interestingly, the formation of highly pure worm-like micelles can be readily monitored by observing the onset of a highly viscous gel in situ due to nanoparticle entanglements occurring during the polymerization. This process thereby allows for a more reproducible synthesis of worm-like micelles simply by monitoring the solution viscosity during the course of the polymerization. In addition, the light stimulus can be intermittently applied in an ON/OFF manner demonstrating temporal control over the nanoparticle morphology.

This article describes a process for producing polymeric self-assembled nanoparticles using visible light mediated dispersion polymerization. Using low energy visible light to control the polymerization allows for the reproducible formation of self-assembled worm-like micelles at high solids content.

Photoredox触媒を用いた可視光媒介分散重合によるワームのようなミセルの簡便な合成

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

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

In this study, an amphiphilic copolymer that includes a core-forming block with phenyl groups was synthesized by living anionic polymerization of phenyl glycidyl ether (PheGE) on methoxy-polyethylene glycol (mPEG-b-PPheGE). Characterization of the copolymer revealed a narrow molecular distribution (PDI &#60; 1.03) and confirmed the degree of polymerization of mPEG122-b-(PheGE)15. The critical micelle concentration of the copolymer was evaluated using an established fluorescence method with the aggregation behavior evaluated by dynamic light scattering and transmission electronic microscopy. The potential of the copolymer for use in drug delivery applications was evaluated in a preliminary manner including in vitro biocompatibility, loading and release of the hydrophobic anti-cancer drug doxorubicin (DOX). A stable micelle formulation of DOX was prepared with drug loading levels up to 14% (wt%), drug loading efficiencies &#62; 60% (w/w) and sustained release of drug over 4 days under physiologically relevant conditions (acidic and neutral pH, presence of albumin). The high drug loading level and sustained release is attributed to stabilizing &#960;-&#960; interactions between DOX and the core-forming block of the micelles.

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

The key steps of living anionic polymerization of phenyl glycidyl ether (PheGE) on methoxy-polyethylene glycol (mPEG-b-PPheGE) are described. The resulting block copolymer micelles (BCMs) were loaded with doxorubicin 14% (wt%) and sustained release of drug over 4 days under physiologically relevant conditions was obtained.

π-πスタッキング相互作用によって安定化されたブロック共重合体ミセルの調製のための両親媒性共重合体のアニオン重合

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

Synthesis of Cyclic Polymers and Characterization of Their Diffusive Motion in the Melt State at the Single Molecule Level

We demonstrate a method for the synthesis of cyclic polymers and a protocol for characterizing their diffusive motion in a melt state at the single molecule level. An electrostatic self-assembly and covalent fixation (ESA-CF) process is used for the synthesis of the cyclic poly(tetrahydrofuran) (poly(THF)). The diffusive motion of individual cyclic polymer chains in a melt state is visualized using single molecule fluorescence imaging by incorporating a fluorophore unit in the cyclic chains. The diffusive motion of the chains is quantitatively characterized by means of a combination of mean-squared displacement (MSD) analysis and a cumulative distribution function (CDF) analysis. The cyclic polymer exhibits multiple-mode diffusion which is distinct from its linear counterpart. The results demonstrate that the diffusional heterogeneity of polymers that is often hidden behind ensemble averaging can be revealed by the efficient synthesis of the cyclic polymers using the ESA-CF process and the quantitative analysis of the diffusive motion at the single molecule level using the MSD and CDF analyses.

A protocol for the synthesis and characterization of diffusive motion of cyclic polymers at the single molecule level is presented.

単一分子レベルでの環状ポリマーの合成と溶融状態におけるそれらの拡散運動のキャラクタリゼーション

We demonstrate a method for the synthesis of cyclic polymers and a protocol for characterizing their diffusive motion in a melt state at the single ...

Synthesis of Plant Phenol-derived Polymeric Dyes for Direct or Mordant-based Hair Dyeing

Effective hair dyeing through in situ incubation of keratin hair with the products of fungal laccase-catalyzed polymerization of plant phenols has been previously demonstrated. However, the dyeing process takes a long time to complete compared to commercial hair-dyeing products. To overcome this bottleneck, pre-synthesized polymeric products of the oxidative reaction of Trametes versicolor laccase on catechin and catechol, either with or without mordant agents (e.g., FeSO4), were here employed to achieve permanent keratin hair dyeing in various colors and shades. The laccase action in acidic sodium acetate buffer led to a deep black coloration after coupling reactions between the plant phenols. The colored dye products were then desalted and concentrated with ultrafiltration. The dyes, with or without mordant agents, caused a significant increase in &#916;E values (i.e., color difference value) in gray human hair within 2.5 hours. In addition, different keratin colors and shades were induced depending upon the mordanting and pH changes. The dyed hair also exhibited a strong resistance to detergent treatments, indicating that our methods can give rise to permanent hair dyeing.&#160;Overall, our work has provided novel insight into developing eco-friendly hair-dyeing methods as alternatives to commercial toxic diamine-based dyes.

Here, we present a protocol to use pre-synthesized polymeric products derived from fungal laccase-catalyzed polymerization of plant phenols, either with or without mordant agents (e.g., FeSO4), to induce detergent-resistant keratin hair dyeing within 2.5 hours.

直接または媒染剤ベースの髪の染色用植物フェノール由来のポリマー染料の合成

Effective hair dyeing through in situ incubation of keratin hair with the products of fungal laccase-catalyzed polymerization of plant phenols has been ...

Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging

Paramagnetic complexes of gadolinium(III) with acyclic or macrocyclic chelates are the most commonly used contrast agents (CAs) for magnetic resonance imaging (MRI). Their purpose is to enhance the relaxation rate of water protons in tissue, thus increasing the MR image contrast and the specificity of the MRI measurements. Current clinically approved contrast agents are low molecular weight molecules that are rapidly cleared from the body. The use of dendrimers as carriers of paramagnetic chelators can play an important role in the future development of more efficient MRI contrast agents. Specifically, the increase in local concentration of the paramagnetic species results in a higher signal contrast. Furthermore, this CA provides a longer tissue retention time due to its high molecular weight and size. Here, we demonstrate a convenient procedure for the preparation of macromolecular MRI contrast agents based on poly(amidoamine) (PAMAM) dendrimers with monomacrocyclic DOTA-type chelators (DOTA &#8211; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate). The chelating unit was appended by exploiting the reactivity of the isothiocyanate (NCS) group towards the amine surface groups of the PAMAM dendrimer to form thiourea bridges. Dendrimeric products were purified and analyzed by means of nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis. Finally, high resolution MR images were recorded and the signal contrasts obtained from the prepared dendrimeric and the commercially available monomeric agents were compared.

Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging

This protocol describes the preparation and characterization of a dendrimeric magnetic resonance imaging (MRI) contrast agent that carries cyclen-based macrocyclic chelates coordinating paramagnetic gadolinium ions. In a series of MRI experiments in vitro, this agent produced an amplified MRI signal when compared to the commercially available monomeric analogue.

調製と<em&gt;インビトロ</em&gt;磁気共鳴イメージングのためのデンドリマーベースの造影剤のキャラクタリゼーション

Paramagnetic complexes of gadolinium(III) with acyclic or macrocyclic chelates are the most commonly used contrast agents (CAs) for magnetic resonance ...