Name: custom-designed laser-based heating apparatus for triggered release of cisplatin from thermosensitive liposomes with magnetic resonance image guidance
Uploaded: 2015-12-13T14:00:00
Description: Watch this Scientific Journal Video about Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance at JoVE

This research is funded by an operating grant from the Canadian Institutes of Health Research (CIHR) to C.A. and D.A.J. The authors acknowledge the Canadian Foundation for Innovation and Princess Margaret Cancer Foundation for funding the STTARR research facility that enables the imaging and therapy research components of this work.

1. Liposomfremstilling <ol><li> Opløs lipiderne 1,2-dipalmitoyl-sn-glycero-3-phosphocholin (DPPC), 1-stearoyl-2-hydroxy-sn-glycero-3-phosphatidylcholin (MSPC eller S-lyso-PC) og N - (carbonyl- methoxypolyethyleneglycol 2000) -1,2-distearoyl- sn-glycero-3-phosphoethanolamin (mPEG 2000 -DSPE) i chloroform. For eksempel til fremstilling af 10 ml HTLC afvejes 314,4 mg DPPC, 39,4 mg MSPC, og 83,9 mg mPEG 2000 -DSPE til en ravfarvet hætteglas. Derefter opløses lip...

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	<li>Maeda, H., Wu, J., Sawa, T., Matsumura, Y., Hori, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tumor+vascular+permeability+and+the+EPR+effect+in+macromolecular+therapeutics:+a+review.">Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review.</a> J Control Releas. 65 (1-2), 271-284 (2000).</li><li>Simard, P., Leroux, J. C., Allen, C., Meyer, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Liposomes+for+Drug+Delivery.">Liposomes for Drug Delivery.</a> Nanoparticles for Pharmaceutical Application. , (2007).</li><li>O'Brien, M. E. 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L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hyperthermia+and+thermosensitive+liposomes+for+improved+delivery+of+chemotherapeutic+drugs+to+solid+tumors.">Hyperthermia and thermosensitive liposomes for improved delivery of chemotherapeutic drugs to solid tumors.</a> Pharm Res. 27 (8), 1750-1754 (2010).</li><li>Viglianti, B. L., 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=In+vivo+monitoring+of+tissue+pharmacokinetics+of+liposome/drug+using+MRI:+illustration+of+targeted+delivery.">In vivo monitoring of tissue pharmacokinetics of liposome/drug using MRI: illustration of targeted delivery.</a> Magn Reson Me. 51 (6), 1153-1162 (2004).</li><li>Ponce, A. 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Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MCML-Monte+Carlo+modeling+of+photon+transport+in+multi-layered+tissues.">MCML-Monte Carlo modeling of photon transport in multi-layered tissues.</a> Comput Meth Prog Bio. 47, 131-146 (1995).</li><li>Rieke, V., Butts Pauly, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MR+thermometry.">MR thermometry.</a> J Magn Reson Imaging. 27 (2), 376-390 (2008).</li><li>Dou, Y. 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Liposomer blev først udviklet i 1960&#39;erne som drug delivery køretøjer, der bærer hydrofile lægemidler i deres interne vandige volumen og hydrofobe stoffer inden for deres lipiddobbeltlag 2. Ud over anvendelse i terapeutiske anvendelser, har liposomer blevet udforsket til diagnostiske anvendelser, når mærket med radionuklider eller fyldt med billeddannende kontrastmidler 17. I de seneste år, Theranostics og terapeutiske-diagnostiske par er blevet forfulgt for at skabe muligheder for bill...

Patofysiologien af ​​faste tumorer resulterer i øget permeabilitet og fastholdelse (EPR), i nanoskala systemer. Dette har ført til udviklingen af mange lægemiddeladministrationssystemer, der udnytter denne virkning til at målrette tumorvævet samtidig minimere systemiske bivirkninger 1. Liposomal levering teknologier er blevet bredt undersøgt for narkotika eller billeddannelse sonder 2. Skønt liposomer betydeligt har reduceret systemisk toksicitet i forhold til konventionel kemoterapi, har der været nogle forbedringer i kliniske effekt 3,4. Undersøgelser har vist, at begrænset effekt skyldes en mangel på lægemiddelfrigivelse fra bæreren 4,5. Som følge heraf er udviklingen af ​​liposomer, der aktiveres til frigivelse af indkapslet lægemiddel som reaktion på ydre stimuli tiltrukket sig betydelig opmærksomhed. Hypertermi har været ansat i årtier som en forholdsvis sikker behandling modalitet for kræftpatienter 6. Derfor udviklerling af termosensitive liposomer med varme som en ekstern trigger har været en logisk kombination med betydeligt potentiale for klinisk oversættelse. Faktisk har lysolipid-holdige varmefølsomt liposom formulering af doxorubicin, kendt som lTSl-DOX, nu nået klinisk evaluering 7. De seneste kliniske data med lTSl-DOX har vist, at protokollen for varme levering er en kritisk faktor, der kan stærkt påvirke patientresultater 8. Hos mennesker er radiofrekvens, mikroovn, laser og ultralydstransducere anvendes til at påføre hypertermi lokalt ved tumor-sites 9. I prækliniske studier, der kræver opvarmning af subkutane tumorer, er opvarmning katetre 10,11 og bade vand 12,13 oftest anvendte. I dette manuskript, introducerer vi en ny metode til opvarmning subkutane tumorer under anvendelse af en specialdesignet laserbaseret opvarmning, som gør, mere konform opvarmning af tumorvolumen. Brug MR kompatible marialer, opsætningen er lille nok til at passe inden i boringen af ​​et lille dyr MR billeddanner, tillader realtidsovervågning af ændringer i væv temperatur under laser opvarmning. MR kontrastmiddel, gadoteridol (Gd-HP-DO3A), blev co-indkapslet med CDDP til en varmefølsom liposom formulering af CDDP (HTLC), kendt som Gd-HTLC, for real-time MR billede-guided overvågning og vurdering af varme -aktiverede medikamentfrigivelse og validering af opvarmningen protokollen. Vores resultater viser, at laser-baserede varme apparat effektivt aktiveret frigivelse af indkapslede agenter fra Gd-HTLC formulering, mens overvåges gennem MR-scanning.

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>Rotary evaporator</td>
			<td>Heidolph Instruments GmbH &#38; Co.KG</td>
			<td>Laborota 4000</td>
			<td></td>
		</tr>
		<tr>
			<td>High pressure extruder</td>
			<td>Northern Lipids Inc.</td>
			<td>T.001</td>
			<td>10 mL thermobarrel</td>
		</tr>
		<tr>
			<td>Heating circulator</td>
			<td>VWR International LLC.</td>
			<td>11305</td>
			<td>Connected to extruder</td>
		</tr>
		<tr>
			<td>Polycarbonate membrane filter</td>
			<td>Whatman</td>
			<td>110605;110606</td>
			<td></td>
		</tr>
		<tr>
			<td>Differential scanning calorimeter (DSC)</td>
			<td>TA Instruments</td>
			<td>Q100</td>
			<td></td>
		</tr>
		<tr>
			<td>Inductively coupled plasma-atomic emission spectrometer (ICP-AES)</td>
			<td>PerkinElmer</td>
			<td>Optima 7300DV</td>
			<td></td>
		</tr>
		<tr>
			<td>Zetasizer</td>
			<td>Malvern Instruments Ltd.</td>
			<td>Nano-ZS</td>
			<td></td>
		</tr>
		<tr>
			<td>Cell incubator</td>
			<td>NuAire Inc.</td>
			<td>NU-5800</td>
			<td></td>
		</tr>
		<tr>
			<td>Autoclip wound clip applier</td>
			<td>Becton Dickinson</td>
			<td>427630</td>
			<td></td>
		</tr>
		<tr>
			<td>Autoclip wound clip remover</td>
			<td>Becton Dickinson</td>
			<td>427637</td>
			<td></td>
		</tr>
		<tr>
			<td>Wound clips</td>
			<td>Becton Dickinson</td>
			<td>427631</td>
			<td>9 mm</td>
		</tr>
		<tr>
			<td>763 nm Laser device</td>
			<td>Biolitec</td>
			<td>Ceralas CD 403 laser</td>
			<td></td>
		</tr>
		<tr>
			<td>Laser probe</td>
			<td>Thorlabs Inc.</td>
			<td>FT400EMT</td>
			<td>With SMA and flat cleave connectors</td>
		</tr>
		<tr>
			<td>Spectralon (illuminator)</td>
			<td>Labsphere Inc.</td>
			<td>FAST-SL-5CMX5CM</td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td>CSTM-SL-5CMX5CM</td>
			<td></td>
		</tr>
		<tr>
			<td>7 Tesla prelinical magnetic resonance (MR) imaging system</td>
			<td>Bruker Corporation</td>
			<td>Biospec 70/30</td>
			<td></td>
		</tr>
		<tr>
			<td>Fiber optic temperature sensor</td>
			<td>LumaSense Technologies Inc.</td>
			<td>Luxtron FOT Lab Kit</td>
			<td></td>
		</tr>
		<tr>
			<td>Integrating sphere</td>
			<td>Newport Corporation</td>
			<td>819C</td>
			<td></td>
		</tr>
		<tr>
			<td>Optical power meter</td>
			<td>Newport Corporation</td>
			<td>1830-R</td>
			<td></td>
		</tr>
	</tbody>
</table>

custom-designed laser-based heating apparatus for triggered release of cisplatin from thermosensitive liposomes with magnetic resonance image guidance

Liposomer er blevet ansat som lægemiddelleveringssystemer at målrette solide tumorer gennem udnyttelse af den forbedrede permeabilitet og fastholdelse (EPR) virkning der resulterer i betydelige reduktioner i systemisk toksicitet. Ikke desto mindre har utilstrækkelig frigivelse af indkapslet lægemiddel fra liposomer begrænset deres kliniske effekt. Temperaturfølsomme liposomer er blevet manipuleret for at tilvejebringe site-specifik frigivelse af lægemiddel med henblik på at overvinde problemet med begrænset tumor lægemiddelbiotilgængelighed. Vores laboratorium har designet og udviklet en varmeaktiveret varmefølsomt liposomformulering af cisplatin (CDDP), kendt som HTLC, at give udløst frigivelse af CDDP ved solide tumorer. Varmeaktiveret levering in vivo blev opnået i murine modeller ved hjælp af en specialbygget laserbaseret varmeapparat, der giver en konform opvarmning mønster ved tumorstedet som bekræftet af MR Temperaturmåling (MRT). En fiberoptisk temperaturovervågningsindretningen blev anvendt til at måle temperaturen i realtidunder hele opvarmningen periode med online justering af varme levering ved skiftevis laser magt. Lægemiddelafgivelse blev optimeret under magnetisk resonans (MR) image vejledning ved co-indkapsling af et MR-kontrastmiddel (dvs. gadoteridol) sammen med CDDP i den varmefølsomme liposomer som et middel til at validere opvarmning protokol og til at vurdere tumorakkumulering. Opvarmningen protokollen bestod af en forvarmning periode på 5 min før indgivelse af HTLC og 20 min opvarmning efter injektion. Denne opvarmning protokol resulterede i en effektiv frigivelse af de indkapslede midler med den højeste MR-signalet observeret ændringer i den opvarmede tumor i sammenligning med den uopvarmede tumor og muskler. Denne undersøgelse viste, vellykket anvendelse af laserbaserede opvarmning apparat til præklinisk termosensitive liposom udvikling og betydningen af ​​MR-vejledt validering af opvarmningen protokol for optimering af lægemiddeladministration.

De HTLC liposomer er fremstillet ved hjælp af fælles metoder, herunder lipid filmdannelse, hydrering, ekstrudering og dialyse. Under trin, der involverer CDDP, bør der udvises forsigtighed for ikke at udsætte CDDP til ethvert aluminium materiale, som CDDP deaktiveres gennem dannelsen af ​​en sort depositum. En illustration af HTLC er vist i figur 3. De fysisk-kemiske egenskaber HTLC blev sammenfattet i et manuskript for nylig offentliggjort i Journal of Controlled Release ...

Watch this Scientific Journal Video about Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance at JoVE

Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance

EN varmeapparat MR-kompatible specialdesignede laserbaseret er blevet udviklet til at give lokal opvarmning af subkutane tumorer for at aktivere frigivelse af agenter fra termosensitive liposomer specifikt mod tumoren regionen.

Custom-designet laser-baserede Varme Apparater til Udløst Frigivelse af cisplatin fra varmefølsom Liposomer med magnetisk resonans billede Vejledning

Liposomes have been employed as drug delivery systems to target solid tumors through exploitation of the enhanced permeability and retention (EPR) effect ...

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