Stable nanoemulsions slide show (ppt)
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Transcript of Stable nanoemulsions slide show (ppt)
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Research sites – SELF-ASSEMBLING NANOEMULSIONS -- data collected mostly at following institutions:
1) Research School of Physical SciencesAustralian National Univ.; Canberra, Australia
2) Dept. of Surgery, Div. of NeurosurgeryUniv. of Connecticut Health Ctr.; Farmington,
CT
3) Dept. of Neurosurgery, Hartford Hospital; CT
( chronology same as “slide order” below ):
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set-up for
Langmuir trough set-up for lipid monolayer analysis ( Stable Nanoemulsions, 2010, 3rd edition, Elsevier, -- [ Fig. 6.1 ] )
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Surface pressure-area curves for a microbubble-surfactant monolayer spread at air/water interface
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Surface pressure-area curves for microbubble surfactant monolayers spread on aqueous phases
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ARTIFICIAL “MIXED-LIPID” NANOEMULSIONS:
• Self-assembly using ONLY NONionic lipids;
• Contains both submicron-sized1) lipid-coated microbubbles, and2) liquid-crystal microparticles
predominantly( and both labeled “LCM” in slides below);
• Lipids employed consist of glycerides, cholesterol, and cholesterol esters (but NOT phospholipids).
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Lipid-coated microbubble histograms (from flow cytometer): A) saturated solution of FilmixTM lipid mixture; B) distilled water alone; C) computed “difference histogram” of LCM.
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Relative size distribution of LCM: Unstirred medium.(Light-scatter signals collected during 1,000-sec period.)
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Relative size distribution of LCM: Stirred medium.(Light-scatter signals collected during 1,000-sec. period.)
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Direct optical imaging of lipid-coated microbubbles (LCM) by phase-measurement interferometric microscopy.
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TARGETED DRUG DELIVERY using a STABLE LIPID NANOEMULSION vehicle:
• Lipid nanoemulsion targets certain “lipoprotein receptors”;
• Drug delivery to target cells is by “ACTIVE uptake” process -- i.e., by ENDOCYTOSIS;
• LCM uptake by target cells is rapid (-- often 2 minutes after i.v. injection in rats).
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Microbubble count contour map. Lipid-coated microbubble (LCM) distribution in tumor -- represented by lines of microbubble isodensity in contour map (bottom right).
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Tumor targeting ability of LCM, after i.v. injection, in rat with liver tumor. (Stained LCM appear here as solid black discs.)
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Confinement of LCM to 9L-gliosarcoma (top left) and to C6-glioma (top right) in rats. Bottom panels show 9L tumor with diO-labeled LCM, in rat, by confocal laser microscopy.
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Interactions of LCM with cultured tumor cells. C6 cells with diO-LCM (panels A,B) or diO alone (panels C,D)
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Kinetics of LCM uptake by tumor cells in culture.( C6 glioma cells incubated with diO-LCM at 3 temper-
atures for periods ranging from 5 to 60 minutes. )
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Localization of diO-LCM in intracellular acidic com-partments. ( C6 tumor cell seen using dual-mode recording for diO [A] and TR stains [B]. Bar = 10 µm)
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Effects of paclitaxel-loaded LCM on the C6-tumor cell morphology. (Control culture [top panel]; paclitaxel [bottom left panel]; paclitaxel-LCM [bottom right].)
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Photomicrograph demonstrating tumor morphology of Sprague-Dawley rats bearing C6 glioma treated with paclitaxel-CRE (A), and paclitaxel- LCM (B, C).
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Photomicrograph demonstrating tumor morphologyof Fischer 344 rats bearing 9L gliosarcomas treatedwith cremophor-LCM (A), and paclitaxel-LCM (B,C).
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Summary of findings on STABLE, MIXED-LIPID,“LCM/nanoparticle-derived” NANOEMULSIONS:
Self-assemble readily from nonionic lipids; Display marked capability for rapid (actively)
targeted chemotherapy; Selective uptake by target cells occurs via
“lipoprotein receptor”-mediated endocyto-sis (particularly via scavenger receptors);
Long-lived (liquid-crystalline) lipid nanostruc-tures predominate in the submicron
range[ cf. particle-size-distribution slides below ].
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