Name: solubility of hydrophobic compounds in aqueous solution using combinations of self-assembling peptide and amino acid
Uploaded: 2017-09-20T14:00:00
Description: Watch this Scientific Journal Video about Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid at JoVE.com

这项工作得到加拿大卫生研究所的支持, MOP-42546 和 MOP-119514 的运作赠款。

1. 氨基酸溶液的制备 <ol> <li> 为每种氨基酸准备和标记两个50毫升圆锥离心管 (分别用于两个和 #34; 低和 #34; 和 #34; 高 #34; 浓度). </li>
	<li> 准备一个大2升瓶, 含纯净水 (18.2 米和 #937; #183; cm 在25和 #176; C). </li>
	<li> 计算每种氨基酸 (克) 达到所需浓度, 并使用刮刀将适当数量的氨基酸称量到各自的50毫升离心管中. 
	注: 对于 #34; 高 #34; 两种带负电荷的氨基酸的浓度, 用 PBS 代替水。由于水的溶解度?...

<ol>
	<li>Holmes, T. C., de Lacalle, S., Su, X., Liu, G., Rich, A., Zhang, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Extensive+neurite+outgrowth+and+active+synapse+formation+on+self-assembling+peptide+scaffolds.">Extensive neurite outgrowth and active synapse formation on self-assembling peptide scaffolds.</a> Proc. Natl. Acad. Sci. U. S. A. 97 (12), 6728-6733 (2000).</li><li>Davis, M. E., Motion, J. P. M., 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=Injectable+self-assembling+peptide+nanofibers+create+intramyocardial+microenvironments+for+endothelial+cells.">Injectable self-assembling peptide nanofibers create intramyocardial microenvironments for endothelial cells.</a> Circulation. 111 (4), 442-450 (2005).</li><li>Matson, J. B., Stupp, S. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-assembling+peptide+scaffolds+for+regenerative+medicine.">Self-assembling peptide scaffolds for regenerative medicine.</a> Chem. Commun. 48 (1), 26-33 (2012).</li><li>Tatman, P. D., Muhonen, E. G., Wickers, S. T., Gee, A. O., Kim, E., Kim, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-assembling+peptides+for+stem+cell+and+tissue+engineering.">Self-assembling peptides for stem cell and tissue engineering.</a> Biomater. Sci. 4 (4), 543-554 (2016).</li><li>Keyes-Baig, C., Duhamel, J., Fung, S. -. Y., Bezaire, J., Chen, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-assembling+peptide+as+a+potential+carrier+of+hydrophobic+compounds.">Self-assembling peptide as a potential carrier of hydrophobic compounds.</a> J. Am. Chem. Soc. 126 (24), 7522-7532 (2004).</li><li>Kumar, P., Pillay, V., Modi, G., Choonara, Y. E., du Toit, L. C., Naidoo, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-assembling+peptides:+implications+for+patenting+in+drug+delivery+and+tissue+engineering.">Self-assembling peptides: implications for patenting in drug delivery and tissue engineering.</a> Recent Pat. Drug Deliv. Formul. 5 (1), 24-51 (2011).</li><li>Wang, H., Yang, Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Short-peptide-based+molecular+hydrogels:+novel+gelation+strategies+and+applications+for+tissue+engineering+and+drug+delivery.">Short-peptide-based molecular hydrogels: novel gelation strategies and applications for tissue engineering and drug delivery.</a> Nanoscale. 4, 5259-5267 (2012).</li><li>French, K. M., Somasuntharam, I., Davis, M. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-assembling+peptide-based+delivery+of+therapeutics+for+myocardial+infarction.">Self-assembling peptide-based delivery of therapeutics for myocardial infarction.</a> Adv. Drug Deliv. Rev. 96, 40-53 (2016).</li><li>Zhang, S., Holmes, T., Lockshin, C., Rich, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spontaneous+assembly+of+a+self-complementary+oligopeptide+to+form+a+stable+macroscopic+membrane.">Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane.</a> Proc. Natl. Acad. Sci. U. S. A. 90 (8), 3334-3338 (1993).</li><li>Bowerman, C. J., Nilsson, B. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-assembly+of+amphipathic+&#946;-sheet+peptides:+insights+and+applications.">Self-assembly of amphipathic &#946;-sheet peptides: insights and applications.</a> Biopolymers. 98 (3), 169-184 (2012).</li><li>Amidon, G., Lennern&#228;s, H., Shah, V., Crison, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+theoretical+basis+for+a+biopharmaceutic+drug+classification:+the+correlation+of+in+vitro+drug+product+dissolution+and+in+vivo+bioavailability.">A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability.</a> Pharm. Res. 12 (3), 413-420 (1995).</li><li>Shi, Y., Porter, W., Merdan, T., Li, L. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+advances+in+intravenous+delivery+of+poorly+water-soluble+compounds.">Recent advances in intravenous delivery of poorly water-soluble compounds.</a> Expert Opin. Drug Deliv. 6 (12), 1261-1282 (2009).</li><li>Bawa, R., Fung, S. -. Y., 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=Self-assembling+peptide-based+nanoparticles+enhance+cellular+delivery+of+the+hydrophobic+anticancer+drug+ellipticine+through+caveolae-dependent+endocytosis.">Self-assembling peptide-based nanoparticles enhance cellular delivery of the hydrophobic anticancer drug ellipticine through caveolae-dependent endocytosis.</a> Nanomedicine. 8 (5), 647-654 (2012).</li><li>Liu, J., Zhang, L., Yang, Z., Zhao, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controlled+release+of+paclitaxel+from+a+self-assembling+peptide+hydrogel+formed+in+situ+and+antitumor+study+in+vitro.">Controlled release of paclitaxel from a self-assembling peptide hydrogel formed in situ and antitumor study in vitro.</a> Int. J. Nanomed. 6, 2143-2153 (2011).</li><li>Wu, Y., Sadatmousavi, P., Wang, R., Lu, S., Yuan, Y., Chen, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-assembling+peptide-based+nanoparticles+enhance+anticancer+effect+of+ellipticine+in+vitro+and+in+vivo.">Self-assembling peptide-based nanoparticles enhance anticancer effect of ellipticine in vitro and in vivo.</a> Int. J. Nanomed. 7, 3221-3233 (2012).</li><li>Fung, S. Y., Yang, H., 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=Self-Assembling+Peptide+as+a+Potential+Carrier+for+Hydrophobic+Anticancer+Drug+Ellipticine:+Complexation,+Release+and+In+Vitro+Delivery.">Self-Assembling Peptide as a Potential Carrier for Hydrophobic Anticancer Drug Ellipticine: Complexation, Release and In Vitro Delivery.</a> Adv. Funct. Mater. 19 (1), 74-83 (2009).</li><li>Fung, S. -. Y., Oyaizu, T., 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=The+potential+of+nanoscale+combinations+of+self-assembling+peptides+and+amino+acids+of+the+Src+tyrosine+kinase+inhibitor+in+acute+lung+injury+therapy.">The potential of nanoscale combinations of self-assembling peptides and amino acids of the Src tyrosine kinase inhibitor in acute lung injury therapy.</a> Biomaterials. 32 (16), 4000-4008 (2011).</li><li>Pacheco, S., Kanou, T., 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=Formulation+of+hydrophobic+therapeutics+with+self-assembling+peptide+and+amino+acid:+A+new+platform+for+intravenous+drug+delivery.">Formulation of hydrophobic therapeutics with self-assembling peptide and amino acid: A new platform for intravenous drug delivery.</a> J. Control. Release. 239, 211-222 (2016).</li></ol>

在制定过程中, 有许多关键步骤和问题需要考虑。首先, 当我们使用不同的组件和浓度时, 整个协议中的多个涡旋步骤确保所有浓度都是一致和正确的。一些高浓度的疏水性氨基酸溶液在涡流后仍可能无法完全溶解, 在这种情况下, 它们可以用手使劲摇动, 以协助过程。同样, sap-AA 解决方案必须经过步骤2.4 中概述的超声步骤, 因为结构调整结构自然倾向于聚合, 而超声将帮助分割 sap 集群, 从而产生更?...

sap 是一类生物材料广泛研究的3D 支架在再生医学1,2,3,4。然而, 最近, 由于其独特的生物学特性5、6、7、8, 它们被作为治疗药物的载体而被利用。sap 自然组装成稳定的纳米结构9, 从而提供了一种药物的封装和保护手段。sap 是亲, 由一个特定的疏水性和亲水性氨基酸重复的模式, 驱动他们的自组装9,10 , 并允许他们作为一个介乎疏水性和亲水性环境.因此, 对于疏水性药物的临床交付--由于在水环境中由于缺乏溶解度而在人体内具有极低的生物利用度和吸收率11,12 -sap 是希望作为交付车辆.此外, 他们的序列模式还意味着, sap 可以合理设计和工程, 以最大限度地与任何特定药物或化合物 (即, 基于功能基团) 的兼容性, 并进一步协助溶解度。
在许多体外和体内设置13、14、15、16中, sap 已被应用为有效的药物运载工具。它们也显示出极大的安全性和生物相容性。然而, 由于低渗透的 SAP 药物制剂, 它们不能用于静脉注射, 在临床设置13。考虑到这种限制, 我们最近制定了一项战略, 将 sap 与氨基酸解决方案结合起来, 以减少毒性 co-solvents 的使用, 并增加处方渗透, 从而提高临床相关性。我们选择使用氨基酸, 因为它们是结构化结构的基石, 已经被临床接受, 并与 sap 结合, 它们增加了疏水性药物的溶解度, 同时减少了需要的17,18的数量。
我们已经审查了 SAP-AA 组合作为一个通用平台的疏水性药物溶解度和后续交付通过创建一个多步骤筛选管道, 并将其应用于 Src 抑制剂, PP2, 作为一个模型疏水性化合物。在这个过程中, 我们研究了改变配方的成分-最终测试6种不同的结构, 所有20种氨基酸在2不同浓度 (低和高; 低根据现有临床应用的浓度, 和高浓度是 2x, 3x, 或5x 的临床浓度的基础上, 每个氨基酸在水中的最大溶解度), 和2不同的 co-solvents-和选择的组合, 溶解 PP2 进一步分析。这种药物制剂在细胞培养中被证明是一种有效的药物载体, 同时也在使用气管和静脉的管理的体内模型。同样, 我们的工作涉及的多功能性的 SAP-AA 组合在磷多, 结构不同的疏水性化合物在水环境中;具体来说, 药物 rottlerin 和姜黄素18。本文概述了液-AA 的配方方法和姜黄素溶解度分析为例, 在我们的筛选管道的主要步骤。该协议提供了一个简单的, 可重现的方式来筛选最佳的 SAP-AA 组合, 它可以溶解任何给定的疏水性化合物。

<table style="border-collapse:collapse;width:1034pt" width="1379">
	<tbody>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">EAK16-I</td>
			<td class="xl17" style="width:106pt" width="141">CanPeptide Inc.</td>
			<td class="xl17" style="width:101pt" width="135">Custom peptide</td>
			<td class="xl20" style="width:510pt" width="680">Sequence: AEAKAEAKAEAKAEAK, N-terminus acetylation and C-terminus amidation, &#62;95% pure by HPLC</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">EAK16-II</td>
			<td class="xl17" style="width:106pt" width="141">CanPeptide Inc.</td>
			<td class="xl17" style="width:101pt" width="135">Custom peptide</td>
			<td class="xl20">Sequence: AEAEAKAKAEAEAKAK, N-terminus acetylation and C-terminus amidation, &#62;95% pure by HPLC</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">EAK16-IV</td>
			<td class="xl17" style="width:106pt" width="141">CanPeptide Inc.</td>
			<td class="xl17" style="width:101pt" width="135">Custom peptide</td>
			<td class="xl20">Sequence: AEAEAEAEAKAKAKAK, N-terminus acetylation and C-terminus amidation, &#62;95% pure by HPLC</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">EFK8-II</td>
			<td class="xl17" style="width:106pt" width="141">CanPeptide Inc.</td>
			<td class="xl17" style="width:101pt" width="135">Custom peptide</td>
			<td class="xl20">Sequence: FEFEFKFK, N-terminus acetylation and C-terminus amidation, &#62;95% pure by HPLC</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">A6KE</td>
			<td class="xl17" style="width:106pt" width="141">CanPeptide Inc.</td>
			<td class="xl17" style="width:101pt" width="135">Custom peptide</td>
			<td class="xl20">Sequence: AAAAAAKE, N-terminus acetylation and C-terminus amidation, &#62;95% pure by HPLC</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">P6KE</td>
			<td class="xl17" style="width:106pt" width="141">CanPeptide Inc.</td>
			<td class="xl17" style="width:101pt" width="135">Custom peptide</td>
			<td class="xl20">Sequence: PPPPPPPKE, N-terminus acetylation and C-terminus amidation, &#62;95% pure by HPLC</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Alanine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">A7469-100G</td>
			<td class="xl20">L-Alanine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Isoleucine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">I7403-100G</td>
			<td class="xl20">L-Isoleucine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Leucine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">L8912-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Leucine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Methionine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">M5308-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Methionine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Proline</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">P5607-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Proline</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Valine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">V0513-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Valine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Phenylalanine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">P5482-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Phenylalanine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Tryptophan</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">T8941-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Tryptophan</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Tyrosine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">T8566-100G</td>
			<td class="xl20">L-Tyrosine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Glycine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">G8790-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Glycine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Asparagine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">A4159-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Asparagine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Glutamine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">G8540-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Glutamine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Serine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">A7219-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Serine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Threonine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">T8441-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Threonine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Histidine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">H6034-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Histidine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Lysine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl17" style="width:101pt" width="135">L5501-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Lysine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Arginine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">A8094-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Arginine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Aspartic Acid</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">A7219-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Aspartic Acid</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Glutamic Acid</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">G8415-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Glutamic Acid</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Cysteine</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">C7352-100G</td>
			<td class="xl17" style="width:510pt" width="680">L-Cysteine</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Dimethyl Sulfoxide</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">D4540-500ML</td>
			<td class="xl22">DMSO</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl17" height="21" style="width:317pt;height:15.75pt" width="423">Ethanol</td>
			<td class="xl17" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl25">277649-100ML</td>
			<td class="xl22">Anhydrous</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl22" height="21" style="height:15.75pt">Curcumin</td>
			<td class="xl21" style="width:106pt" width="141">Sigma-Aldrich</td>
			<td class="xl22">08511-10MG</td>
			<td class="xl22">Hydrophobic drug, curcumin</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl22" height="21" style="height:15.75pt">Rottlerin</td>
			<td class="xl21" style="width:106pt" width="141">EMD Millipore</td>
			<td class="xl22">557370-10MG</td>
			<td class="xl22">Hydrophobic drug, rottlerin</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl21" height="21" style="width:317pt;height:15.75pt" width="423">PP2</td>
			<td class="xl21" style="width:106pt" width="141">Enzo&#160;</td>
			<td class="xl22">BML-EI297-0001</td>
			<td class="xl21" style="width:510pt" width="680">Hydrophobic drug, PP2</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl21" height="21" style="width:317pt;height:15.75pt" width="423">Scintillation Vials</td>
			<td class="xl21" style="width:106pt" width="141">VWR</td>
			<td class="xl21" style="width:101pt" width="135">2650-66022-081</td>
			<td class="xl22">Borosilicate Glass, with Screw Cap, 20 mL. Vials for weighing peptide.</td>
		</tr>
		<tr height="21" style="height:15.75pt">
			<td class="xl21" height="21" style="width:317pt;height:15.75pt" width="423">Falcon 50 mL Conical Centrifugation Tubes</td>
			<td class="xl21" style="width:106pt" width="141">VWR</td>
			<td class="xl23" style="width:101pt" width="135">352070</td>
			<td class="xl22">Polypropylene, Sterile, 50 mL. For amino acid solutions.</td>
		</tr>
	</tbody>
</table>

solubility of hydrophobic compounds in aqueous solution using combinations of self-assembling peptide and amino acid

自组装多肽 (sap) 是有前途的车辆提供疏水疗法的临床应用;它们的亲特性使它们能够在人体的水环境中溶解疏水化合物。然而, 自肽解决方案有较差的血液相容性 (例如, 低渗透), 阻碍了他们的临床应用通过静脉注射管理。我们最近开发了一个通用的疏水药物输送平台, 它将 sap 与氨基酸溶液 (液-AA) 结合起来, 提高药物的溶解度, 增加配方渗透, 达到临床使用的要求。在三种不同的疏水性化合物--PP2、rottlerin 和姜黄素--的背景下, 对这种配方进行了彻底的测试, 以证明其通用性。此外, 我们研究了改变配方成分的影响, 分析了6种不同的结构, 20 种天然氨基酸在低和高浓度, 和两个不同的 co-solvents 二甲基亚砜和乙醇。我们的策略被证明是有效的, 以优化一个给定的疏水性药物的成分, 和治疗功能的配方抑制剂, PP2, 被观察到的体外和在体内。这篇手稿概述了我们的通用配方方法使用 SAP-AA 组合疏水性化合物, 并分析溶解度作为第一步, 以潜在使用这些配方在更多的功能性研究。我们包括有代表性的溶解度结果的配方疏水性化合物, 姜黄素, 并讨论如何作为一个平台, 未来的生物研究和疾病模型的方法。

对于疏水性药物, 姜黄素, 我们生产的配方使用所有20种天然存在的氨基酸在低浓度, 结合只有一个 SAP, EAK16-II, 作为一个原理。我们还测试了使用二甲基亚砜和乙醇作为 co-solvents 的配方。总的, 这产生了40姜黄素配方, 每个含有不同的成分。重要的是要注意, 在我们以前的研究使用 Src 抑制剂, PP2, 我们包括更多的选择的 SAP (共 6) 和氨基酸浓度 (临床, 以及较高的浓度), 这产生?...

Watch this Scientific Journal Video about Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid at JoVE.com

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid

自组装肽与氨基酸结合的水溶液中疏水性化合物的溶解度

本议定书描述了一种临床适用的方法, 溶解疏水化合物在水环境中使用自肽和氨基酸溶液的组合。我们的方法解决疏水疗法的一个主要局限, 缺乏安全, 有效的手段溶解和交付方法入临床设置。

Self-assembling peptides (SAPs) are promising vehicles for the delivery of hydrophobic therapeutics for clinical applications; their amphipathic ...

Research

Education

JoVE Journal

JoVE Core

Organic Chemistry

Medicine

Unit 1

Covalent Bonding and Structure

SCIENTISTS IN ACTION

Assessment of Gastric Emptying in Non-obese Diabetic Mice Using a [13C]-octanoic Acid Breath Test

Assessment of Gastric Emptying in Non-obese Diabetic Mice Using a [13C]-octanoic Acid Breath Test

使用的非肥胖型糖尿病小鼠胃排空的评估[<sup&gt; 13</sup&gt; C-辛酸呼气试验

Gastric emptying studies in mice have been limited by the inability to follow gastric emptying changes in the same animal since the most commonly used ...

科研

医学

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury

在实验颈脊髓损伤协同使用神经前体细胞，并自组装肽的

Spinal cord injuries (SCI) cause serious neurological impairment and psychological, economic, and social consequences for patients and their families. ...

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport

使用多氟化胆汁酸和<em&gt;在体内</em&gt;磁共振成像来衡量胆汁酸运输

Along with their traditional role as detergents that facilitate fat absorption, emerging literature indicates that bile acids are potent signaling ...

Estimation of Nephron Number in Whole Kidney using the Acid Maceration Method

酸化浸渍法评价全肾肾素数

Nephron endowment refers to the total number of nephrons an individual is born with, as nephrogenesis in humans is completed by 36 weeks of gestation and ...

Rapid Evaluation of Toxicity of Chemical Compounds Using Zebrafish Embryos

利用斑马鱼胚胎对化合物毒性的快速评价

The zebrafish is a widely used vertebrate model organism for the disease and phenotype-based drug discovery. The zebrafish generates many offspring, has ...

Using a Chemical Biopsy for Graft Quality Assessment

使用化学活检进行移植质量评估

Kidney transplantation is a life-saving treatment for a large number of people with end-stage renal dysfunction worldwide. The procedure is associated ...

On-Site Sampling and Extraction of Brain Tumors for Metabolomics and Lipidomics Analysis

代谢组学和利皮多米分析脑肿瘤的现场采样与提取

Despite the variety of tools available for cancer diagnosis and classification, methods that enable fast and simple characterization of tumors are still ...

Preparation of Naringenin Solution for In Vivo Application

Preparation of Naringenin Solution for In Vivo Application

柚皮素溶液的制备

The preparation of a compound (phytochemical) solution is an overlooked but critical step prior to its application in studies such as drug screening. The ...

Evaluation of Amino Acid Consumption in Cultured Bone Cells and Isolated Bone Shafts

Bone development and homeostasis is dependent upon the differentiation and activity of bone forming osteoblasts. Osteoblast differentiation is ...

Visualizing and Quantifying Pharmaceutical Compounds within Skin using Coherent Raman Scattering Imaging

使用相干拉曼散射成像对皮肤内的药物化合物进行可视化和定量

Cutaneous pharmacokinetics (cPK) after topical formulation application has been a research area of particular interest for regulatory and drug development ...