Limit size lipid nanoparticles and related methods

a technology of lipid nanoparticles and limit size nanoparticles, which is applied in the direction of granular delivery, flow mixers, powder delivery, etc., can solve the problems of limited sample contamination, sample degradation, and inability to produce systems smaller than approximately 50 nm,

Inactive Publication Date: 2014-11-06
THE UNIV OF BRITISH COLUMBIA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0035]FIG. 5 illustrates the effect of the POPC/TO molar ratio on the size of LNPs. Nanoemulsions based on different POPC/TO ratios (see Table 1) were produced at FRR=3 (3 ml/min for the aqueous stream, 1 ml/min for the ethanolic stream, total lipid concentr...

Problems solved by technology

Methods of making limit size LNP have not progressed substantially for nearly 30 years.
The preferred method for making bilayer vesicles in the 100 nm size range involves extrusion of preformed multilamellar vesicles (micron size range) through polycarbonate filters with a pore size of 100 nm or smaller and is not useful for producing systems smaller th...

Method used

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  • Limit size lipid nanoparticles and related methods
  • Limit size lipid nanoparticles and related methods
  • Limit size lipid nanoparticles and related methods

Examples

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example 1

Preparation and Characterization of Representative LNP

[0187]In this example, the preparation and characterization of representative LNP are described.

[0188]Lipids and Chemicals.

[0189]1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) was obtained from Avanti Polar Lipids (Alabaster, Ala.). 1,2,3-Tri(cis-9-octadecenoyl) glycerol (glyceryl trioleate, TO), cholesterol (Chol), sodium chloride, ammonium sulfate, and doxorubicin hydrochloride were from Sigma-Aldrich Canada Ltd. (Oakville, Ontario, Canada).

[0190]Micromixer Design and Fabrication.

[0191]The micromixer was a chaotic mixer for continuous flow systems with the layout based on patterns of asymmetric grooves on the floor of the channel (staggered herringbone design) that induce a repeated sequence of rotational and extensional local flows thus inducing rapid mixing of the injected streams. The device was produced by soft lithography, the replica molding of microfabricated masters in elastomer. The device features a 200 μm wi...

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Abstract

Various lipid nanoparticles are disclosed, including nanoparticles comprising a lipid bilayer comprising a phospholipid, a sterol, a polyethylene glycol-lipid surrounding an aqueous core which comprises a therapeutic and/or diagnostic agent and nanoparticles comprising a lipid monolayer surrounding a hydrophobic core. Of particular interest are limit size lipid nanoparticles with a diameter from 10-100 nm. Such lipid nanoparticles are the smallest particles possible for a specific particle composition. Methods and apparatus for preparing such limit size lipid nanoparticles are disclosed.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application claims the benefit of U.S. Patent Application No. 61 / 551,366, filed Oct. 25, 2011, expressly incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]The present invention is directed to limit size nanoparticles for delivery of therapeutic and / or diagnostic agents, methods for using the lipid nanoparticles, and methods and systems for making the lipid nanoparticles.BACKGROUND OF THE INVENTION[0003]The ability to produce the smallest particles possible (the “limit size”) from lipid components is important for applications ranging from drug delivery to the production of cosmetics. In the area of drug delivery, for example, size is an important determinant of the biodistribution of lipid nanoparticles (LNP) following intravenous (i.v.) injection. Long-circulating LNP of diameter 100 nm or smaller are able to preferentially accumulate at disease sites such as tumors and sites of infection and inflammation d...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K47/44A61K31/704A61K9/127A61K49/00
CPCA61K9/14A61K9/127A61K47/44A61K31/704A61K49/0002A61K9/1075A61K9/1271A61K9/1277Y10T428/2982A61P1/08A61P23/00A61P25/08A61P25/24A61P33/06A61P35/00A61P43/00A61P9/06A61P9/12B01F23/41B01F25/431B01F25/431971B01F25/4331B01F33/30B01F25/4317A61J3/00B01L3/502715B01L3/50273B01L2200/0605B01L2200/0647B01L2300/06B01L2300/0848B01L2300/0867B01L2300/18
Inventor CULLIS, PIETER R.JIGALTSEV, IGOR V.TAYLOR, JAMES R.LEAVER, TIMOTHYWILD, ANDREBELLIVEAU, NATHAN MAURICE
Owner THE UNIV OF BRITISH COLUMBIA
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