Lipid nanoparticle (lnp) encapsulation of mrna products
AssigneeNature's Toolbox, Inc.
InventorAlexander Koglin
Life of this patent
Estimating the term…
Abstract
The invention includes a novel microfluidic mixing chip configured for the production of lipid nano-particles (LNPs) and in particular LNPs encapsulating oligonucleotides, such as mRNA that may be used in various therapeutic applications such as vaccines and the like.
Claims52
A microfluidic chip comprising:
- at least one lipid insertion channel configured to direct a flow of a lipid solution containing a quantity of oligonucleotides;
- one or more buffer channels configured to direct a flow of a buffer solution;
- an inlet junction positioned at the intersection of the lipid insertion and buffer channels;
- a mixing channel in fluid communication with said inlet junction and configured to direct a flow of a lipid and buffer solution to an outlet channel, wherein said mixing channel includes one or more of:
- a meander channel in fluid communication with said inlet junction and configured to direct a flow of the lipid and buffer solution to an outlet channel;
- one or more hairpin turns in fluid communication with said inlet junction and configured to direct a flow of the lipid and buffer solution to an outlet channel;
- and
- wherein said lipid solution, as it is passes through said mixing channel, forms a plurality of lipid nano-particles (LNPs) encapsulating the oligonucleotides;
- and
- a receiving container configured to collect said LNPs.
The microfluidic chip of any claim above wherein said LNPs have a particle size between 420 nanometers (nm) and 82 nm.
The microfluidic chip of any claim above wherein said LNPs have an encapsulation efficiency of at least 71%.
The microfluidic chip of any claim above wherein said LNPs are lyophilized.
A pharmaceutical composition containing a LNP of any claim above.
A method of producing lipid nano-particles (LNPs) comprising the steps:
- establishing a microfluidic mixing chip having a lipid insertion channel and one or more buffer channels;
- directing a lipid solution containing a quantity of oligonucleotides through said lipid insertion channel;
- directing a buffer solution through said one or more buffer channels;
- mixing said lipid solution containing a quantity of oligonucleotides and said buffer solution at an inlet junction;
- directing said solution through a mixing channel having one or more of:
- a meander channel in fluid communication with said inlet junction and configured to direct a flow of the lipid and buffer solution to an outlet channel;
- one or more hairpin turns in fluid communication with said inlet junction and configured to direct a flow of the lipid and buffer solution to an outlet channel;
- and
- forming a plurality of LNPs encapsulating the oligonucleotides;
- and
- collecting and optionally isolating said LNPs.
The method of any claim above wherein said LNPs have a particle size between 420 nanometers (nm) and 82 nm.
The method of any claim above wherein said LNPs have an encapsulation efficiency of at least 71%.
The method of any claim above and further comprising the step of lyophilizing said LNPs.
A pharmaceutical compositions containing a LNP produced by the method of any claim above.
A microfluidic chip for the production of lipid nano-particles (LNPs) having one or more meander channels and/or hairpin turns.
A lipid solution for the production of lipid nano-particles (LNPs) comprising:
- a cationic lipid comprising dimethyldioctadecylammonium bromide (DDAB),
- a neutral lipid comprising 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC),
- a sterol/lipid comprising cholesterol (CHOL), and
- a cosurfactant comprising 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol (PEG-DMG).
A microfluidic mixing chip for the production of lipid nano-particles (LNPs) having:
- at least one lipid insertion channel;
- one or more buffer channels;
- an inlet junction;
- a mixing channel fluid, wherein said mixing channel optionally includes one or more of:
- a meander channel;
- and
- one or more hairpin turns.
Dependencies are inferred from the claim text.