Name: encapsulation of cancer therapeutic agent dacarbazine using nanostructured lipid carrier
Uploaded: 2016-04-26T14:00:00
Description: Watch this Scientific Journal Video about Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier at JoVE.com

Han anerkjenner at Saudi Arabia finansierte stipend (I821) for å gjøre forskningen mulig. Forfatterne er takknemlige for Dr Xianwei Liu for kompetansestøtte i TEM-analyse ved Cranfield University.

1. Fremstilling av olje-i-vann-emulsjon <ol><li> Veie glyserylpalmitostearat (120 mg), isopropylmyristat (60 mg), d-α-tocopheryl polyetylenglykol suksinat (30 mg) og soyabønne lecitin (30 mg), og legge dem til 12,5 ml av organiske løsningsmidler (6,25 ml aceton og 6,25 ml etanol). Raskt å oppløse blandingen ved temperaturen 70 ° C (5 ° C over smeltepunktet av det faste lipid) i vannbad. </li><li> Tilsett enten 125, 250 eller 375 mg av Poloxamer188 i 12,5 ml DDH 2 O for å oppnå 1-3% (henholdsvis) av...

<ol>
	<li>Loo, T. L., Housholder, G. E., Gerulath, A. H., Saunders, P. 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F., Gohla, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterisation+of+a+novel+solid+lipid+nanoparticle+carrier+system+based+on+binary+mixtures+of+liquid+and+solid+lipids.">Characterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids.</a> Int J Pharm. 199 (2), 167-177 (2000).</li><li>M&#252;ller, R. H., Radtke, M., Wissing, S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nanostructured+lipid+matrices+for+improved+microencapsulation+of+drugs.">Nanostructured lipid matrices for improved microencapsulation of drugs.</a> Int J Pharm. 242 (1-2), 121-128 (2002).</li><li>Pouton, C. 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K., 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=Thymoquinone-loaded+nanostructured+lipid+carrier+exhibited+cytotoxicity+towards+breast+cancer+cell+lines+(MDA-MB-231+and+MCF-7)+and+cervical+cancer+cell+lines+(HeLa+and+SiHa).">Thymoquinone-loaded nanostructured lipid carrier exhibited cytotoxicity towards breast cancer cell lines (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa).</a> BioMed Research International. , (2015).</li><li>Sun, 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=Quercetin-nanostructured+lipid+carriers:+Characteristics+and+anti-breast+cancer+activities+in+vitro.">Quercetin-nanostructured lipid carriers: Characteristics and anti-breast cancer activities in vitro.</a> Colloids Surf., B. 113, 15-24 (2014).</li><li>Savla, R., Garbuzenko, O. B., Chen, S., Rodriguez-Rodriguez, L., Minko, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tumor-Targeted+Responsive+Nanoparticle-Based+Systems+for+Magnetic+Resonance+Imaging+and+Therapy.">Tumor-Targeted Responsive Nanoparticle-Based Systems for Magnetic Resonance Imaging and Therapy.</a> Pharm Res. 31 (12), 3487-3502 (2014).</li><li>Chen, 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=Formulation,+characterization,+and+evaluation+of+in+vitro+skin+permeation+and+in+vivo+pharmacodynamics+of+surface-charged+tripterine-loaded+nanostructured+lipid+carriers.">Formulation, characterization, and evaluation of in vitro skin permeation and in vivo pharmacodynamics of surface-charged tripterine-loaded nanostructured lipid carriers.</a> Int J Nanomedicine. 7, 3023 (2012).</li><li>Sanna, V., Caria, G., Mariani, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+lipid+nanoparticles+containing+fatty+alcohols+having+different+chain+length+on+the+ex+vivo+skin+permeability+of+Econazole+nitrate.">Effect of lipid nanoparticles containing fatty alcohols having different chain length on the ex vivo skin permeability of Econazole nitrate.</a> Powder Technol. 201 (1), 32-36 (2010).</li><li>Brigger, I., Dubernet, C., Couvreur, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Nanoparticles+in+cancer+therapy+and+diagnosis.">Nanoparticles in cancer therapy and diagnosis.</a> Adv Drug Deliv Rev. 54 (5), 631-651 (2002).</li><li>Visaria, R. 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Lipidbaserte nanostrukturerte partikler er blitt benyttet for å tilveiebringe en høyt lipofil bærer for avgivelse av hydrofobe legemidler. En NLC er den andre generasjonen av fast lipid nanostrukturerte bærer, som er faste ved romtemperatur og ved kroppstemperatur. Inkorporering av et fast lipid inn i en flytende lipid i en NLC resulterer i en mindre perfekt krystalliseringen, og dermed øke den medikament-last effektivitet og også redusere utvisning av innkapslede stoffer under lagring. <p class="jove_content"...

Dakarbazin (Dac) er et alkyleringsmiddel som utøver antitumoraktivitet gjennom nukleinsyrer metylering eller direkte DNA-skade, som fører til cellesyklus-stans og celledød 1. Som et første linje kjemoterapeutisk middel, har Dac vært brukt alene eller i kombinasjon med andre kjemoterapeutiske medikamenter for behandling av forskjellige kreftformer 2-6. Det er det mest aktive middel hittil anvendt i behandling av kutan og metastatisk melanom, som er den mest aggressive formen for hudkreft 3,7,8. Responsraten er imidlertid bare 20% i beste fall, og den terapeutiske effekten er ofte ledsaget av alvorlige systemiske bivirkninger. I sin naturlige form, er Dac hydrofil og er ustabil på grunn av sin foto 9. Den eneste tilgjengelige formel for klinisk bruk for tiden er et sterilt pulver som skal brukes i suspensjon for intravenøs infusjon 7,8. Den lave svarprosenten og høy systemisk toksisitet rspiste av stoffet er i stor grad tilskrives den dårlige løselighet i vann, derfor lav tilgjengelighet på målområde, og høy distribusjon på non-target områder, noe som begrenser den maksimale dosen av stoffet 10. Den hurtige nedbrytning og metabolisme etter intravenøs opptak sammen med utviklingen av medikamentresistens begrenser den kliniske anvendelsen og terapeutisk effekt av legemidlet 11. Derfor er det et presserende behov for å utvikle alternative Dac formuleringer for behandling av malignt melanom. Kolloidale systemer som inneholder liposomer, har miceller eller nanostrukturerte partikler blitt intensivt undersøkt for deres bruk i levering av legemidler som vurderes av Marilene et al. 12 nanostrukturerte partikler som potensielle legemiddelbærere har vært å tiltrekke økt oppmerksomhet i det siste tiåret på grunn av deres evne til å øke narkotika lasting effektivitet, kontroll narkotika utgivelse, forbedre narkotika farmakokinetikk og biodistribusjon, og derfor reduce narkotika systemisk toksisitet 13. Bare noen få nanoformulations har imidlertid vært så langt for Dac levering undersøkt, som viser beskyttelse av medikamentet fra bildet degenerasjon, øket oppløselighet medikament, og forbedret terapeutisk effekt 10,14,15. Men disse formuleringene led av lav innkapslingspolymeren effektivitet, mens noen også bruke syntetiske polymernanopartikler som ikke er kostnadseffektivt. Nanostrukturerte lipid bærere (NLC), laget av en blanding av fast og flytende lipider, har blitt utviklet for levering av legemidler 16,17. Medikamentene som skal innkapsles ofte er løselige i både væske- lipider og faste lipider faser 18, noe som resulterer i en høy lasting og kontrollert frigivelse 19. Denne studien tar sikte på å utvikle en ny Dac formulering basert på NLC-innkapsling hjelp glycerylpalmitostearat og isopropylmyristat som lipider. Fremstillingen involvert olje-i-vann-emulsjon, fordampning, størkning, og homogenization. Forberedelsene har vært preget av NLC størrelse, form, ultrastructure, og dispersitet, narkotika innkapsling effektivitet og narkotika lasting 20.

<table border="0" cellpadding="0" cellspacing="0" width="968">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Dacarbazine (DAC)</td>
			<td style="width:467px;">Sigma Aldrich (Gillingham Dorset, UK)</td>
			<td style="width:119px;">D2390-100MG</td>
			<td style="width:167px;">drug used for uploading</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">glyceryl palmitostearate&#160;</td>
			<td>Gattefoss&#233; (Saint_Priest_c&#233;dex, France)</td>
			<td style="width:119px;">85251-77-0</td>
			<td>solid lipid&#160;</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">d-&#945;- Tocopherol polyethylene glycol succinate (TPGS)</td>
			<td>Sigma Aldrich (Gillingham Dorset, UK)</td>
			<td style="width:119px;">57668</td>
			<td>lipid phase surfactant</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Poloxamer 188</td>
			<td>Sigma Aldrich (Gillingham Dorset, UK)</td>
			<td style="width:119px;">15759-1KG</td>
			<td>liqiud phase surfactant</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Acetone&#160;</td>
			<td>Sigma Aldrich (Gillingham Dorset, UK)</td>
			<td style="width:119px;">650501-1L</td>
			<td>organic solvent</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Ethanol&#160;</td>
			<td>Sigma Aldrich (Gillingham Dorset, UK)</td>
			<td style="width:119px;">459836-1L</td>
			<td>organic solvent</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Soybean lecithin (SL)</td>
			<td>Cuisine Innovation (Dijon, France)</td>
			<td style="width:119px;">SLL1402</td>
			<td>lipid phase surfactant</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:216px;">Double-distilled water was collected in our laboratory from</td>
			<td>Millipore-Q Gradient A10 ultra-pure water system (Millipore, France)</td>
			<td style="width:119px;">SAS - 67120&#160;</td>
			<td>aqueous phase&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">T 25 digital ULTRA-TURRAX</td>
			<td style="width:467px;">IKA</td>
			<td style="width:119px;">3725000</td>
			<td>as high shear disperser</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:216px;">Hotplate Magnetic Stirrer</td>
			<td>Scientific Support, Inc</td>
			<td style="width:119px;">1454&#160;</td>
			<td>emulsion homogenization</td>
		</tr>
	</tbody>
</table>

encapsulation of cancer therapeutic agent dacarbazine using nanostructured lipid carrier

Den eneste formel dakarbazin (DAC) i klinisk anvendelse er intravenøs infusjon, presentere en dårlig terapeutisk profil på grunn av den lave dispersitet av medikamentet i vandig oppløsning. For å overvinne dette, ble en nanostrukturerte lipidbærer (NLC) bestående av glyserylpalmitostearat og isopropylmyristat utviklet for å innkapsle Dac. NLCS med kontrollert størrelse ble oppnådd ved anvendelse av høy skjærkraft dispersjon (HSD) etter størkning av olje-i-vann-emulsjon. Syntese parametere, inkludert overflateaktivt middel-konsentrasjon, hastighet og tid for HSD ble optimalisert for å oppnå den minste NLC med størrelse, polydispersion indeks og zeta-potensial på 155 ± 10 nm, 0,2 ± 0,01, og -43,4 ± 2 mV, respektivt. De optimale parametere ble også benyttet for Dac-lastet NLC forberedelse. Den resulterende NLC lastet med Dac besatt størrelse, polydispersion indeks og zeta potensial på 190 ± 10 nm, 0,2 ± 0,01, og -43,5 ± 1,2 mV, henholdsvis. Stoffet innkapsling efyteevne og medikament-last nådde 98% og 14%, respektivt. Dette er den første rapport om innkapsling av Dac ved hjelp NLC, noe som tyder på at NLC kan være en ny potensiell kandidat som legemiddelbærer for å forbedre den terapeutiske profilen av Dac.

Forberedelsene av NLC og NLC-Dac bruker glycerylpalmitostearat og isopropylmyristat med ulike parametere ble preget for PS, PDI, morfologi og ultrastructure 20. PS og PDI av NLCS var surfaktant konsentrasjon, HSD hastighet og varighet avhengig. Som bedømt av PS og PDI av NLCS, ble de beste resultatene oppnådd med 1% av overflateaktivt middel og en ren dispersjon hastighet på 15.000 rpm i 30 minutter (figur 1 A, B og C), som...

Watch this Scientific Journal Video about Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier at JoVE.com

Encapsulation of Cancer Therapeutic Agent Dacarbazine Using Nanostructured Lipid Carrier

Den mest brukte metode for nanostrukturerte lipidbærer (NLC) syntese omfatter olje-i-vann-emulsjon, homogenisering og størkning. Dette ble endret her ved å bruke høy skjær spredning etter størkning for å oppnå en NLC med ønskelig størrelse, forbedret narkotika innkapsling og narkotika lasteeffektivitet som en potensiell bærer for dacarbazine levering.

Innkapsling av kreft Terapeutisk Agent dacarbazine Bruke Nanostrukturerte Lipid Carrier

The only formula of dacarbazine (Dac) in clinical use is intravenous infusion, presenting a poor therapeutic profile due to the low dispersity of the drug ...

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Chemistry

Untargeted Metabolomics from Biological Sources Using Ultraperformance Liquid Chromatography-High Resolution Mass Spectrometry (UPLC-HRMS)

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A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl

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The serine protease Granzyme B (GzmB) mediates target cell apoptosis when released by cytotoxic T lymphocytes (CTL) or natural killer (NK) cells. GzmB is ...

The Bioconjugation and Radiosynthesis of 89Zr-DFO-labeled Antibodies

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Den Bioconjugation og radiosynthesis av<sup&gt; 89</sup&gt; Zr-DFO-merkede antistoffer

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Facile Utarbeidelse av Internt Selv montert Lipid Partikler Stabilisert av karbonnanorør

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Mass spectrometry (MS) is one of the most commonly used technologies for quantifying proteins in complex samples, with excellent assay specificity as a ...

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