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

Dette arbeidet er støttet av kanadiske institutter for helseforskning, gir drift MOPP-42546 og MOPP-119514.

1. forberedelse av aminosyre løsninger <ol><li>forberede og etikett to 50 mL konisk sentrifuge rør for hver aminosyre (en for begge &#34; lav &#34; og &#34; høy &#34; konsentrasjoner).</li>
	<li>Lage en stor 2 L kolbe med renset vann (18.2 MΩ·cm ved 25 ° C).</li>
	<li>Beregne hvor mye hver aminosyre (i gram) for å nå de ønskede konsentrasjonene og veie riktig mengde aminosyre i deres respektive 50 mL sentrifuge rør ved hjelp av en slikkepott. 
	Merk: Hvis den &#34; høy &#34; konsentrasjon av to negativ...

<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>

I formulering prosedyren er det ulike avgjørende skritt og punkter for å vurdere i feilsøking. Først, som vi arbeider med ulike komponenter og konsentrasjoner, flere vortex trinn gjennom protokollen sikrer at alle konsentrasjoner er uniform og korrekt. Noen av høy-konsentrasjon, hydrofobe aminosyre løsningene fortsatt helt oppløses ikke etter vortexing, og i dette tilfellet kan de rokkes kraftig av assisterer i prosessen. Likeledes er det viktig at SAP-AA løsninger gjennomgå sonication trinnet skissert i trinn 2...

Saper er en klasse av biologisk materiale som har blitt studert grundig som 3D stillaser i regenerativ medisin1,2,3,4. Flere nylig imidlertid har de blitt utnyttet som kjøretøy for leveranse av therapeutics på grunn av sin unike biologiske egenskaper5,6,7,8. Saper naturlig samle inn stabil nanostrukturer9, gir et middel for narkotika innkapsling og beskyttelse. Saper er amphipathic, består av et bestemt mønster av hydrofobe og hydrofile aminosyre gjentas, kjøre deres selvtillit forsamlingen9,10 og tillater dem å tjene som et medium mellom hydrofobe og hydrofile miljøer. Derfor for klinisk levering av hydrofobe narkotika-som har ekstremt lav bioavailability og absorpsjon i kroppen på grunn av løselighet i vandig miljøer11,12 -SAPer er lovende som en levering kjøretøy. Videre innebærer sine sekvens mønster også at safter kan rasjonelt designet og konstruert for å maksimere kompatibilitet med alle gitt narkotika eller sammensatte (dvs., basert på funksjonelle grupper) og videre hjelpe oppløselighet.
Saper er brukt som effektive levering biler i mange i vitro og vivo innstillinger13,14,15,16. De har også vist stor sikkerhet og biocompatibility. Men på grunn av lav osmolaritet SAP-stoff forberedelser, kan ikke de brukes for intravenøs injeksjoner som klinisk innstillinger13. Vurderer denne tvang, vi har nylig utviklet en strategi som kombinerer safter aminosyre løsninger for å redusere bruken av giftige co løsemidler og øke formulering osmolaritet, og derfor kliniske relevans. Vi valgte å bruke aminosyrer som de er byggesteinene i safter, er allerede klinisk akseptert, og i kombinasjon med safter, de øker hydrofobe narkotika løselighet mens redusere SAP kreves17,18.
Vi har gransket SAP-AA kombinasjoner som en generalisert plattform for hydrofobe narkotika løselighet og senere levering ved å opprette en flertrinns screening rørledning og bruke det på den Src inhibitor, PP2, som en modell hydrofobe compound. I denne prosessen undersøkte vi effekten av skiftende komponenter av utformingen-slutt testing 6 forskjellige safter, alle 20 aminosyrer i 2 ulike konsentrasjoner (lav og høy, lav basert på konsentrasjoner i eksisterende klinisk bruk, og høy konsentrasjoner var 2 x, 3 x eller 5 x klinisk konsentrasjonen basert på maksimal Løseligheten av hver aminosyre i vann), og 2 forskjellige co løsemidler – og utvalgte kombinasjoner som solubilized PP2 for videre analyse. Denne drug formulering viste seg for å være effektiv som et stoffet levering kjøretøy i cellekultur, samt i vivo modeller med både intratracheal og intravenøs administrasjoner. Likeledes, arbeidet rørt på allsidigheten av SAP-AA kombinasjoner i solubilizing flere strukturelt-ulike hydrofobe forbindelser i vandig miljøer. spesielt narkotika rottlerin og curcumin18. Dette manuskriptet skisserer SAP-AA formulering metoden og analyse av curcumin løselighet som et eksempel på det viktigste trinnet i våre screening rørledningen. Denne protokollen gir optimal SAP-AA kombinasjonene, som oppløse alle gitt hydrofobe sammensatte reproduserbar enkelt til skjermen.

<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

Selv av peptider (tjenestetilgang) er lovende biler for levering av hydrofobe therapeutics for klinisk bruk; amphipathic egenskaper tillate dem å oppløse hydrofobe forbindelser i vandig miljøet i menneskekroppen. Men selv montasje peptid løsninger har fattig blod kompatibilitet (f.eks, lav osmolaritet) hindre deres klinisk anvendelse gjennom intravenøs administrasjoner. Vi har nylig utviklet en generalisert plattform for hydrofobe narkotika-leveranser, som kombinerer safter aminosyre løsninger (SAP-AA) for å forbedre narkotika løselighet og øke formulering osmolaritet å nå kravene for klinisk bruk. Denne formuleringen strategien ble grundig testet i forbindelse med tre strukturelt forskjellige hydrofobe forbindelser-PP2, rottlerin og curcumin-for å demonstrere sin allsidighet. Videre undersøkte vi effekten av skiftende formulering komponenter ved å analysere 6 forskjellige safter, 20 naturlig eksisterende aminosyrer i lave og høye konsentrasjoner, og to forskjellige co løsemidler dimethyl sulfoxide (DMSO) og etanol. Vår strategi viste seg for å være effektive i å optimalisere en gitt hydrofobe narkotika og terapeutisk funksjon av den formulerte inhibitor, PP2, ble observert både i vitro og i vivo. Dette manuskriptet skisserer våre generalisert formulering metoden ved hjelp av SAP-AA kombinasjoner for hydrofobe forbindelser og analyse av løselighet som et første skritt mot potensielle bruk av disse formuleringene i mer funksjonelle studier. Vi inkluderer representant løselighet resultater for utformingen av den hydrofobe sammensatte, curcumin, og diskutere hvordan vår metode fungerer som en plattform for fremtidige biologiske studier og sykdom modeller.

For hydrofobe stoffet, curcumin, produsert vi formuleringer bruker alle 20 naturlig eksisterende aminosyrer i lave konsentrasjoner i kombinasjon med bare én SAP, EAK16-II, som et bevis-av-prinsippet. Vi testet formuleringer hjelp DMSO og etanol co løsemidler. I alt produsert dette 40 curcumin formuleringer, hver med ulike komponenter. Det er viktig å merke seg at i våre tidligere studier bruker Src inhibitor, PP2, vi inkludert flere alternativer for SAP (totalt 6) og aminosyre konsent...

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

Løseligheten av hydrofobe forbindelser i vandig løsning ved hjelp av kombinasjoner av selvstendig montering peptid og aminosyre

Denne protokollen beskriver en klinisk-aktuelt måte oppløsende hydrofobe forbindelser i en vandig miljø med kombinasjoner av selvstendig montering peptid og aminosyre løsninger. Vår metode løser en stor begrensning av hydrofobe therapeutics, mangler, effektive middel til løselighet og levering i klinisk innstillinger.

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

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