Limit size lipid nanoparticles and related methods

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...

AI Technical Summary

Benefits of technology

The invention provides limit size lipid nanoparticles that can be used for delivering therapeutic and diagnostic agents to a subject. These nanoparticles have a diameter of about 10 to about 100 nm and are stable in aqueous environments. The nanoparticles can be made using a device that includes a first inlet for receiving a first solution, a second inlet for receiving a second solution, and a third microchannel for receiving the first and second solutions. The nanoparticles can also be made by flowing the first and second solutions through a plurality of microchannels. The invention also provides methods for making and using the nanoparticles. The technical effects of the invention include improved delivery of therapeutic and diagnostic agents, increased solubility of drugs, and reduced side effects.

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 than approximately 50 nm.

The predominant method for making limit size systems has usually involved sonication of multilamellar vesicles, usually tip sonication, which has limitations of sample contamination, sample degradation and, most importantly, lack of scalability.

However the production of stable systems with size ranges less than 50 nm has proven elusive.

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