Compounds for encapsulation and delivery

Abstract

The present invention relates to a novel compound, an ionizable lipid, an ionizable lipid nanoparticle, a method of producing such an ionizable lipid, a method of producing such an ionizable lipid nanoparticle, an ionizable lipid and an ionizable lipid nanoparticle obtainable by such a method, a composition comprising said compound or ionizable lipid or ionizable lipid nanoparticle, as well as the use of such a compound, ionizable lipid, ionizable lipid nanoparticle or composition for medical treatment and / or prevention and for further areas of application.

Description

[0001] Munich, 9 January 2026

[0002] Our Ref.: SM 7019-03WO CMC / fmo / gas

[0003] Applicant: SyVento sp. z o. o

[0004] Serial Number: New Application

[0005] SyVento sp. z o. o

[0006] ul. Za gorq 19, 32-050 SKAWINA, POLAND

[0007] Compounds for encapsulation and delivery

[0008] Technical Field

[0009] The present invention relates to a novel compound, an ionizable lipid, an ionizable lipid nanoparticle, a method of producing such an ionizable lipid, a method of producing such an ionizable lipid nanoparticle, an ionizable lipid and an ionizable lipid nanoparticle obtainable by such a method, a composition comprising said compound or ionizable lipid or ionizable lipid nanoparticle, as well as the use of such a compound, ionizable lipid, ionizable lipid nanoparticle or composition for medical treatment and / or prevention and for further areas of application.

[0010] Background of the invention

[0011] Delivering an active ingredient to a specific target site has been of great importance in research for decades. To provide the best effect possible it was found to be mandatory the active ingredient to be part of a formulation that manages to get exactly to the place where it is needed to be released, absorbed or distributed and to act specifically. On this way the active ingredient needs to be protected from possible destruction. At best, high bioavailability and low toxicity to the target organism should be ensured. Therefore, amphiphilic molecules were deemed to be effective delivery systems for molecules. More than just serving as delivery system they can also be used as main ingredient to target specific areas or receptors. Many small molecules are easily destructible, if not protected, but should nevertheless be transported to a specific location to take effect there. It was found that nanoparticles have useful properties for this purpose. They can increase the bioavailability of such molecules, transport substances specifically to their site of action and

[0012] - with the aid of certain surfactants - even cross the blood-brain barrier for specific drug targeting.

[0013] Having both, lipophilic and hydrophilic parts, also liposomes and microemulsions are often used as delivery system. Therefore, appropriate compounds such as lipids are useful. Nanocrystals, nanospheres and nanocapsules are more examples of molecule delivery systems. Containing lipid structures combined with the characteristics of nanoparticles, makes lipid nanoparticle (LNP) technology gaining significant importance. Due to the insight to be among the most effective molecule delivery systems it is especially used in the field of nucleic acid delivery, such as mRNA, siRNA, linear DNA, antisense nucleotide, oligonucleotide, aptamer, miRNA and pDNA, for gene therapy, e.g. in combination with the CRISPR-Cas9 method, and mRNA vaccines. Also in fields like cosmetics, nutrition, the agricultural sector, protein replacement, self-replicating, CAR-T cell therapy, in-vivo cell therapy, immunotherapy and cancer therapy an increasing use is possible.

[0014] As a special form of lipid nanoparticles prove to be ionizable lipid nanoparticles and the ionizable lipids contained therein. These lipids, due to their ability to change charge depending on the pH, enable effective encapsulation, protection, and delivery of small molecules like nucleic acids to target locations, such as cells, for example.

[0015] Contemporary LNP systems rely on ionizable lipids with specific chemical structures that can acquire a positive charge in acidic environments, which is crucial for their function. At neutral or basic pH, these lipids are neutral, minimizing their toxicity, while in acidic environments, such as endosomes, they ionize. That means at low pH the positive charges of the lipid ensure binding to a negatively charged basis. E.g. in case of binding to the negatively charged mRNA, the positively charged ionizable lipids promote endosomal membrane destabilization and the release of the payload into the cytoplasm. Along with further lipids, the ionizable lipids form a protective envelope around the sensitive molecules, such as nucleic acids, and thus ensure that they can be safely and efficiently introduced into target locations.

[0016] A famous application of such LNP technology is the ionizable lipid D-Lin-MC3-DMA which is used in Patisiran, commercially used as Onpatro®. Patisiran is a drug for the treatment of hereditary ATTR amyloidosis (hATTR), based on RNA interference, a so-called siRNA. That means, siRNA has been encapsulated in a LNP to be protected and delivered to aspecial target location, in this case a mRNA region of the target organism coding for a protein called transthyretin.

[0017]

[0018] SM-102 by Modema® and ALC-0315 by BioNTech® / Pfizer® are further prominent examples for ionizable lipids and their use in LNP technology. They have been used in formulations for mRNA based vaccines against Covid-19.

[0019]

[0020] ALC-0315

[0021] D-Lin-MC3-DMA, SM-102 and ALC-0315 all disclose a chemical structure comprising an aliphatic tertiary amine as the ionizable part. Along with one or two ester groups there are disclosed aliphatic hydrocarbon chains. All of these structures do not disclose any aromatic structure at all. While D-Lin-MC3-DMA, SM-102 and ALC-0315 are all used to encapsulate and deliver a specific siRNA or mRNA and are made exclusively for one specific medical treatment or in one pharmaceutical composition, respectively, literature and current practice are completely silent about further formulations and uses.

[0022] US 11 ,766,408 B2 discloses ionizable lipids and SORT (selecting organ targeting) lipids that are permanently protonated as well as compositions comprising them. Apart from D-Lin-MC3-DMA the ionizable lipids disclosed may comprise cyclic hydrocarbon compounds, mainly heteroaryl or heterocycloalkyl groups, while they hardly comprise benzoic structures, nor hydroxyhydroquinone structures. Most lipid chains connected to an ester group disclosed in said patent are exactly connected to the carbon atom of the ester group.In certain embodiments, the aliphatic amine is connected to non-conjugated alkenyl groups as tail groups disclosed. According to the patent, the ionizable lipids can be used to deliver a composition for delivery of a therapeutic agent such as a nucleic acid, a protein or a small molecule to a particular organ. An alternative target organism or further payload let alone other uses are not mentioned.

[0023] WO 2021 / 055833 A1 discloses specific compounds, compositions, empty and loaded LNPs and methods, and describes branched tail lipid compounds and compositions for intracellular delivery therapeutic agents. The chemical structures have mainly aliphatic lipids, while a possible cyclic and aromatic group is directly connected to the oxygen atom of an ester group and the carbon chain between the aliphatic amine and the ester group is directly connected to the carbon atom of the ester group. A hydroxyhydroquinone structure is not disclosed or suggested. The document does not mention any further use than the medical or therapeutic one.

[0024] The article of Tang et al., “Ionizable Lipid Nanoparticles for mRNA Delivery”, 2023, concentrates on mRNA delivery in ionizable LNPs and discloses several ionizable lipids. Among them there is D-Lin-MC3-DMA. Beside other aliphatic lipid groups there are also shown aromatic groups, wherein a benzene can be connected to an ester group either directly to an oxygen atom or via a methylene group. In this special example, the ionizable lipid called ssPalmO-Phe also has a disulfide bridge. The article is silent on hydroxybenzoic acid or hydroxyhydroquinone structures. All disclosed ionizable LNPs and the ionizable lipids used therein are exclusively used for mRNA delivery in a therapeutical field, the article is completely silent about further uses.

[0025] Considering the advantageous effects and immense possibilities of the LNP technology in general and the compounds used therein, there is a continuous need to search for new ionizable lipid structures and even completely new chemical structural classes of lipids suitable as ionizable lipids. The goal is to improve the efficiency of molecule delivery to specific locations in versatile target organisms, whether it is the human body with its usual cell structure, skin barrier and even beyond the blood-brain barrier. Also other organisms than the human body can be target organisms like, e.g., plant cells due to the great capability of compounds suitable as ionizable lipids and whole ionizable LNPs passing through biomembranes. Therefore, there is need for new ionizable lipids and LNP formulations in further application areas than just immune modulation or drug targeting in the therapeutic field, such as cosmetics, nutrition and the agricultural sector. Besides, it is required by new compounds suitable as ionizable lipids as both, autonomous mainingredient and preferably as carrier lipid, to have a high bioavailability and to be easily tissue compatible. There is further a need of compounds suitable as ionizable lipids being able to reduce toxicity for the target organism and to increase the stability of LNP formulations with the aim of protecting the main ingredient and the formulation itself. Combining these desirable properties in one single lipid could lead to be able to use stable and highly functional compounds, LNPs or compositions for an immensely wide range of applications.

[0026] Summary of the invention

[0027] The present invention solves the above needs by providing, in a first aspect, a compound being represented by formula (A) or formula (B) or formula (C) or a salt or stereoisomer thereof, preferably being suitable as lipid, particularly preferably being used as ionizable lipid

[0028]

[0029] formula (A),

[0030] wherein n is 1 , 2, 3, 4, 5 or 6, preferably 1 , 2, 3 or 4, more preferably 2 or 3,

[0031] wherein Ri is an alkyl, a conjugated alkenyl, or an alkinyl, and

[0032] wherein R2 is selected from the group consisting of H, COOH, benzyl, phenol, an alkyl, and a conjugated alkenyl, and

[0033] wherein R3 and R4 are independently selected from the group consisting of H, NH2, benzyl, phenol, benzoic acid, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, an alkyl, and an alkenyl, andwherein Rs is selected from the group consisting of H, NH2, an alkyl, an alkenyl or an alkinyl, or

[0034]

[0035] formula (B),

[0036] wherein Re is represented by formula (B-1)

[0037]

[0038] formula (B-1),

[0039] or a salt or stereoisomer thereof, and

[0040] wherein m is 1 , 2, 3, 4, 5 or 6, preferably 2, 3, 4 or 5, particularly preferably 2 or 5, and

[0041] wherein R7 is represented by formula (B-1) or a salt or stereoisomer thereof, or is selected from the group consisting of H, an alkyl with a total number of carbon atoms in the range from 1 to 7, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group, and

[0042] wherein Rs is represented by formula (B-1) or a salt or stereoisomer thereof, or is selected from the group consisting of H, an alkyl with a total number of carbon atoms in the range from 1 to 7, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group or a propanol group, and

[0043] wherein R9 is selected from the group consisting of H, O-RBI or an alkyl,wherein RBI is H or an alkyl, and, when RBI is an alkyl, RBI has a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14 or 15, and

[0044] wherein Rio is selected from the group consisting of H, O-RB2 or an alkyl,

[0045] wherein RB2 is H or an alkyl, and

[0046] wherein Rn is selected from the group consisting of H, O-RB3 or an alkyl,

[0047] wherein RB3 is H or an alkyl, and, when RB3 is an alkyl, RB3 has a total number of carbon atoms of 1 , 2, 3 or 4 and / or wherein m is 5 and / or wherein Rio is O-RB2, and when Rio is O-RB2, RB2 is an alkyl with a total number of carbon atoms of 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, and

[0048] wherein R12 is selected from the group consisting of H, O-RB4 or an alkyl,

[0049] wherein RB4 is H or an alkyl, and

[0050] preferably wherein at least one of R9, R10, R11 or R12 is selected from the group consisting of O-RBI, O-RB2, O-RB3 or O-RB4, or

[0051]

[0052] formula (C),

[0053] wherein k is 1 , 2, 3, 4, 5 or 6, preferably 2, 3, 4 or 5, particularly preferably 2 or 3, and

[0054] wherein R13 is an alkyl, an alkenyl or an alkinyl, and

[0055] wherein R14 is selected from the group consisting of H, a benzyl, an alkyl or an alkenyl, and

[0056] wherein R15 is selected from the group consisting of H, a methanol group, an ethanol group, a propanol group, a butanol group, a pentanol group or an alkyl, andwherein Ri6 is selected from the group consisting of H, an ethanol group, a propanol group, a butanol group, a pentanol group or an alkyl.

[0057] In one embodiment, there is provided a compound according to the first aspect, wherein the tertiary amine being represented as N in formula (A) or formula (B) or formula (C) is selected from the group of a tertiary aliphatic amine, a tertiary cyclic amine and a tertiary aromatic amine, preferably wherein the at least one tertiary amine is a tertiary cyclic amine or a tertiary aliphatic amine, particularly preferably a tertiary aliphatic amine.

[0058] In another embodiment, there is provided a compound according to the first aspect, wherein further at least one of Ri, R2, R5, R9, R10, R11 and R12 is / are an alkyl, an alkenyl or an alkinyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, preferably with a total number of carbon atoms in the range from 6 to 24, more preferably wherein at least one of R1, R2, R5, R9, R10, R11 and R12 has a total number of carbon atoms of 10, 12, 13, 15, 16, 17 or 18,

[0059] wherein the Ri-alkenyl and / or the R2-alkenyl is / are a conjugated alkenyl, preferably a conjugated alkenyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above,

[0060] and / or wherein at least one of RBI, RB2, RB3 and RB4 is / are (an) alkyl(s).

[0061] In yet another embodiment, there is provided a compound according to the first aspect, wherein further the alkyl representing RBI, RB2, RB3 and / or RB4 comprises one or more hetero atoms as chemical residue, preferably wherein the hetero atom(s) is / are oxygen atom(s),

[0062] wherein R9 comprises a sole ether group being O-RBI as defined in formula (B-1 ), wherein R10 comprises a sole ether group being O-RB2 as defined in formula (B-1), wherein Rn comprises a sole ether group being O-RB3 as defined in formula (B-1), and / or wherein R12 comprises a sole ether group being O-RB4 as defined in formula (B-1).

[0063] In a further embodiment, there is provided a compound according to the first aspect being represented by formula (1), (2), (3), (4), (5), (6), (7), (8), (9), (11), (12), (13), (14), (18), (19), (20), (21), (22), (23), (24), (25), (26) or (27) or a salt or stereoisomer thereof, preferably being suitable as lipid, particularly preferably being used as ionizable lipid

[0064]

[0065] formula (3),

[0066]

[0067] HO

[0068] formula (5),

[0069]

[0070] formula (9),

[0071]

[0072] formula (12),

[0073]

[0074] formula (15),

[0075]

[0076] formula (16),

[0077]

[0078] formula (19),

[0079]

[0080] formula (22),

[0081]

[0082] formula (23),

[0083]

[0084] formula (27).

[0085] In a second aspect, there is provided an ionizable lipid according to the first aspect and the various embodiments related thereto, comprising a hydroxybenzoic acid structure,wherein one tertiary amine is present and

[0086] wherein the tertiary amine has at least one chemical residue, wherein the chemical residue is selected from the group consisting of H, an alkyl, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group, a butyl group or a propanol group, or

[0087] wherein the tertiary amine is a tertiary cyclic amine, preferably the being present as part of a pyrrolidine, a piperidine, a pyrrole or a pyridine structure, preferably a pyrrolidine or piperidine, and

[0088] wherein not more than two ester groups are present, wherein the carboxyl group of the hydroxybenzoic acid has an alkyl, a conjugated alkenyl or an alkinyl as chemical residue, and wherein the tertiary amine is connected to the phenolic oxygen atom of the hydroxybenzoic acid via an alkyl group, or

[0089] wherein the ionizable lipid has a chemical structure of formula (A) as defined above, or

[0090] wherein the ionizable lipid has a chemical structure of formula (B), wherein formula (B) includes formula (B-1), as defined above.

[0091] In one embodiment, there is provided an ionizable lipid according to the second aspect, wherein one or two hydroxybenzoic acid(s) is / are present,

[0092] preferably wherein the aromatic group of the hydroxybenzoic acid has H, an ether or an alkyl as a chemical residue,

[0093] preferably wherein the tail group as chemical residue of the ether and / or the aromatic group of the hydroxybenzoic acid and / or the oxygen atom of the carboxyl group is an alkyl, an alkenyl or an alkinyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, more preferably with a total number of carbon atoms in the range from 6 to 24, particularly preferably with a total number of carbon atoms of 10, 12, 13, 15, 16, 17 or 18.

[0094] In a third aspect, there is provided an ionizable lipid according to the first aspect and the various embodiments related thereto, comprising a hydroxyhydroquinone structure,preferably wherein the ionizable lipid has a chemical structure of formula (C) as defined above,

[0095] wherein one tertiary amine is present and

[0096] wherein the tertiary amine has at least one chemical residue, wherein the chemical residue is selected from the group consisting of H, an alkyl, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group, a butyl group or a propanol group, or

[0097] wherein the tertiary amine is a tertiary cyclic amine, preferably the being present as part of a pyrrolidine, a piperidine, a pyrrole or a pyridine structure, preferably a pyrrolidine or piperidine, and

[0098] wherein the tertiary amine is connected to the oxygen atom in position 4 of the hydroxyhydroquinone structure according to IUPAC nomenclature via an alkyl group,

[0099] preferably wherein the two oxygen atoms in positions 1 and 2 of the hydroxyhydroquinone structure according to IUPAC nomenclature are connected via a carbon atom, more preferably wherein the connecting carbon atom has at least one alkyl with a total number of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, as chemical residue, particularly preferably with a total number of carbon atoms of 13.

[0100] In a fourth aspect, there is provided a method of producing the compound according to the first aspect and the various embodiments related thereto, or the lipid according to the second aspect and the embodiments related thereto, or the lipid according to the third aspect and the embodiments related thereto,

[0101] wherein the method comprises the following steps, in sequence:

[0102] a) providing a raw material comprising a structure of hydroxbenzoic acid or a derivative or a salt thereof or a structure of hydroxyhydroquinone or a derivative or a salt thereof,

[0103] b) mixing the provided raw material with a substance for elongating the tail group of the provided raw material,c) adding a substance to the mixture obtained in b) for hydrating a derivative of a hydroxyl group of the mixture obtained in b),

[0104] d) adding a substance comprising a tertiary amine to the mixture obtained in c), and

[0105] e) obtaining a product comprising a hydroxybenzoic acid or hydroxyhydroquinone structure connected to a tertiary amine and further comprising a lipophilic tail group as defined above.

[0106] In a fifth aspect, there is provided an ionizable lipid nanoparticle comprising the compound according to the first aspect and the various embodiments related thereto or the lipid according to the second aspect and the embodiments related thereto.

[0107] In one embodiment, there is provided an ionizable lipid nanoparticle according to the fifth aspect, further comprising,

[0108] structure lipids, wherein the structure lipid is phospholipid and / or sphingolipid, preferably wherein the phospholipid is selected from the group consisting of PC, PE, PA, PG, PI, PS and LPL, preferably wherein the sphingolipid is sphingomyelin, more preferably wherein the phospholipid is selected from the group of DSPC, DOPE, HSPC, DPPC, DSPG, DSPS and DPPA,

[0109] sterols, preferably wherein the sterol is cholesterol and / or sitosterol,

[0110] lipids modified with hydrophilic polymers, preferably wherein the lipid modified with hydrophilic polymers is PEGylated lipid, more preferably wherein the PEGylated lipid is DMG-PEG and / or DSPE-PEG and / or DSG-PEG,

[0111] and optionally

[0112] SORT lipids, preferably wherein the SORT lipid comprises DODAP, DOTAP, DPDAB, DODMA, 14PA, 18BMP, 18PA, DC-cholesterol and / or 5A2-SC8,

[0113] and optionally

[0114] antioxidants and / or oils and / or fatty acids and / or fatty acid salts and / or surfactants.In a sixth aspect, there is provided a method of producing the ionizable lipid nanoparticles according to the fourth aspect and the embodiments related thereto,

[0115] wherein the method comprises the following steps, in sequence:

[0116] a) providing a lipid phase comprising a compound according to the invention, an ionizable lipid according to the invention or a product obtained according to the invention,

[0117] b) providing an aqueous phase,

[0118] c) mixing the lipid phase provided in a) with the aqueous phase provided in b),

[0119] preferably wherein a microfluidic technique is used, and

[0120] d) obtaining a lipid nanoparticle.

[0121] In a seventh aspect, there is provided a composition comprising the compound according to the first aspect and the various embodiments related thereto or the ionizable lipid according to the second aspect and the embodiments related thereto or the ionizable lipid nanoparticle according to the fourth aspect and the embodiments related thereto,

[0122] preferably wherein the composition is a pharmaceutical composition, a cosmetic composition, a nutritional composition or an agricultural composition.

[0123] In an eighth aspect, there is provided a compound according to the first aspect, or an ionizable lipid according to the second or third aspect, or an ionizable lipid nanoparticle according to fifth aspect, or a composition according to the seventh aspect, for use in a method of treatment and / or prevention as an active ingredient or as a cargo of an active ingredient.

[0124] In a ninth aspect, there is provided a compound according to the first aspect, or an ionizable lipid according to the second or third aspect, or an ionizable lipid nanoparticle according to fifth aspect, or a composition according to the seventh aspect, for use in a method of treatment and / or prevention as an active ingredient or as a cargo of an active ingredient,wherein at least one disease selected from the group of cancer, inflammatory diseases, autoimmune diseases, destroyed tissue, psychological disorders, gastrointestinal diseases and respiratory diseases is / are treated and / or prevented.

[0125] In a variant aspect according to the eighth aspect, there is provided a use of the compound according to the first aspect and the various embodiments related thereto or a use of the ionizable lipid according to the second aspect and the embodiments related thereto or of the ionizable lipid according to the third aspect and the embodiments related thereto or a use of the ionizable lipid nanoparticle according to the fifth aspect and the embodiments related thereto or a use of the composition according to the seventh aspect for the manufacture or preparation of a medicament for treatment and / or prevention of a disease or health condition as an active ingredient or as a cargo of an active ingredient.

[0126] In a variant aspect according to the ninth aspect, there is provided a use of the compound according to the first aspect and the various embodiments related thereto or a use of the ionizable lipid according to the second aspect and the embodiments related thereto or of the ionizable lipid according to the third aspect and the embodiments related thereto or a use of the ionizable lipid nanoparticle according to the fifth aspect and the embodiments related thereto or a use of the composition according to the seventh aspect for the manufacture or preparation of a medicament for treatment and / or prevention of a disease or health condition as an active ingredient or as a cargo of an active ingredient,

[0127] wherein at least one disease selected from the group of cancer, inflammatory diseases, autoimmune diseases, destroyed tissue, psychological disorders, gastrointestinal diseases and respiratory diseases is / are treated and / or prevented.

[0128] In a variant aspect according to the eighth and ninth aspect there is provided a method of treatment or prevention of a disease or health condition, comprising administering a compound or an ionizable lipid or an ionizable lipid nanoparticle or a composition according to the various aspects to a patient in need thereof. Optionally, said method comprises administering a pharmaceutically acceptable carrier or excipient.

[0129] In one embodiment the disease to be treated or prevented is cancer. In another embodiment the disease to be treated or prevented is an inflammatory disease. In yet another embodiment the disease to be treated or prevented is an autoimmune disease. In a further embodiment the health condition to be treated or prevented is destroyed tissue. In yet a further embodiment the disease to be treated or prevented is a psychologicaldisorder. In still another embodiment the disease to be treated or prevented is a gastrointestinal disease. In an even further embodiment the disease to be treated or prevented is a respiratory disease.

[0130] In a tenth aspect, there is provided a use of the compound according to the first aspect and the various embodiments related thereto or the ionizable lipid according to the second or third aspect and the embodiments related thereto or the ionizable lipid nanoparticle according to the fifth aspect and the embodiments related thereto or the composition according to the seventh aspect as a cargo in a cosmetic product, in a nutritional product, in a diagnostic product, for recombinant protein production, or in an agricultural product.

[0131] Brief description of drawings

[0132] The term “Lipid G” or “SYV-G” as used herein and specifically in the figures refers to formula (1) according to the invention. The term “Lipid O” or “SYV-O” or “LO” or “SYV-014” as used herein and specifically in the figures refers to formula (2) according to the invention. The term “Lipid P” or “SYV-P” or “LP” or “SYV-015” as used herein and specifically in the figures refers to formula (3) according to the invention. The term “Lipid S” or “SYV-S” or “SYV-017” as used herein and specifically in the figures refers to formula (4) according to the invention. The term “Lipid C” or “SYV-C” as used herein and specifically in the figures refers to formula (5) according to the invention. The term “Lipid E” or “SYV-E” as used herein and specifically in the figures refers to formula (6) according to the invention. The term “Lipid F” or “SYV-F” or “LF” as used herein and specifically in the figures refers to formula (7) according to the invention. The term “Lipid H” or “SYV-H” as used herein and specifically in the figures refers to formula (8) according to the invention. The term “Lipid K” or “SYV-K” as used herein and specifically in the figures refers to formula (9). The term “Lipid M” or “SYV-M” as used herein and specifically in the figures refers to formula (10) according to the invention. The term “Lipid N” or “SYV-N” as used herein and specifically in the figures refers to formula (11) according to the invention. The term “Lipid R” or “SYV-R” or “SYV-016” as used herein and specifically in the figures refers to formula (12) according to the invention. The term “Lipid U” or “SYV-U” or “SYV-019” as used herein and specifically in the figures refers to formula (13) according to the invention. The term “Lipid W” or “SYV-W” or “SYV-020” as used herein and specifically in the figures refers to formula (14) according to the invention. The term “Lipid T” or “SYV-T” or “SYV-018” as used herein and specifically in the figures refers to formula (15) according to the invention. The term “Lipid X” or “SYV-X” or “SYV-021” as used herein and specifically in the figures refers to formula (18) according to the invention. The term “SYV-026” as used herein and specifically in the figures refers to formula (19) according to the invention. The term “SYV-029” as used herein and specifically in thefigures refers to formula (20) according to the invention. The term “Lipid Y” or“SYV-Y” or “SYV-022” as used herein and specifically in the figures refers to formula (21) according to the invention.

[0133] Figure 1 (Fig. 1) shows the in-vivo distribution of mRNA-LNPs via bioluminescence imaging. 6-8 week-old female BALB / c mice were administered dispersion of provided test formulations. As a result the accumulation and decay of bioluminescence associated with the administered mRNA-LNP formulations can be seen with the help of luciferin. The representative IVIS images show groups of female BALB / c mice injected with 5 pg Luc mRNA encapsulated by LNP formulations, comprising Lipid F and Lipid G, by the intravenous route after 24h after administration.

[0134] Figure 2 (Fig. 2) shows the in-vivo distribution of mRNA-LNPs via bioluminescence imaging. 6-8 week-old female BALB / c mice were administered dispersion of provided test formulations. As a result the accumulation and decay of bioluminescence associated with the administered mRNA-LNP formulations can be seen with the help of luciferin. The representative IVIS images show groups of female BALB / c mice injected with 5 pg Luc mRNA encapsulated by LNP formulations, comprising Lipid O and Lipid P, by the intravenous route after 24h after administration.

[0135] Figure 3 (Fig. 3) shows the bioluminescent signal shown in Fig. 1 and Fig. 2 quantified as total flux (p / s). For a better understanding the signals are compared to a group of mice that were administered LNP formulations comprising the ionizable lipid SM-102.

[0136] Figure 4 (Fig. 4) shows IC50 (half maximal Inhibitory Concentration) values of ionizable lipids according to the invention plus, for better illustration, an IC50 value of ionizable lipid SM-102 in comparison. The higher the value, the lower is the cytotoxicity of the ionizable lipid.

[0137] Figure 5 (Fig. 5) shows a bar plot representing a Jurkat luminescence readout [RLU] after 24 hours of treatment. There are shown formulations according to the invention and lipofectamine transfection in an amount of 50 ng, 20 ng and 10 ng of mRNA per well, respectively. Lipofectamine transfection showed such a low luminescence, that the column is almost not visible here. For a better understanding the values of Lipid P, Lipid O and Lipid G are compared to formulations comprising the ionizable lipid SM-102. Error bars represent SD values.Figure 6 (Fig. 6) shows a bar plot representing a Jurkat luminescence readout [RLU] divided by non-transfected cells luminescence readout after 24 hours of treatment. There are shown formulations according to the invention and lipofectamine transfection in an amount of 50 ng mRNA per well. For a better understanding the values of Lipid P, Lipid O and Lipid G are compared to formulations comprising the ionizable lipid SM-102. Error bars represent SD values.

[0138] Figure 7 (Fig. 7) shows a bar plot representing the ratio between formulations according to the invention, namely Lipid P, Lipid O and Lipid G, compared to SM-102 in an amount of 50 ng mRNA per well, respectively.

[0139] Figure 8 (Fig. 8, A and B) shows the efficiency of siRNA transfection in LNPs according to the invention, more specifically expression of Target mRNA (TNC) forsiRNA-LNP in U-87 MG (Glioma) Cells Compared to Empty LNPs. Incubation for 48 Hours in the Presence of 5% FBS. The lower the value, the better. The expression values comprising LNPs according to the invention as a cargo for nucleic acids are compared to control values of LNPs that do not have an active ingredient. The decimal numbers written on the x-axis represent the concentration of siRNA in the respective LNP in pg / mL for a comparison of target silencing levels in different concentrations. The target is Tenascin-C (TNC). 8A shows LNPs comprising lipid MC3. 8B shows LNPs comprising lipid C12-200. The expression of target mRNA (TNC) forsiRNA-LNP in U-87 MG (Glioma) cells are compared to empty LNPs that comprise the same lipid composition, but do not have a payload, as control LNPs. E.g. SYV1 and SYV6 comprise the same lipid composition and were prepared at the same lipid concentration, but differ in having a payload or not. The incubation was carried out for 48 hours in Presence of 5% FBS. The lower the value, the better is the target silencing effectiveness. The level of gene expression silencing was calculated relative to the corresponding control LNP.

[0140] Figure 9 (Fig. 9, A and B) shows the efficiency of siRNA transfection in LNPs according to the invention, more specifically expression of Target mRNA (TNC) forsiRNA-LNP in U-87 MG (Glioma) Cells Compared to Empty LNPs. Incubation for 48 Hours in the Presence of 5% FBS. The lower the value, the better. The expression values comprising LNPs according to the invention as a cargo for nucleic acids are compared to control values of LNPs that do not have an active ingredient. The decimal numbers written on the x-axis represent the concentration of siRNA in the respective LNP in pg / mL for a comparison of target silencing levels in different concentrations. The target is TNC. 9A shows LNPs comprising Lipid F. 9B shows LNPs comprising Lipid O. The expression of target mRNA(TNC) for siRNA-LNP in U-87 MG (Glioma) cells are compared to empty LNPs that comprise the same lipid composition, but do not have a payload, as control LNPs. E.g. SYV3 and SYV8 comprise the same lipid composition and were prepared at the same lipid concentration, but differ in having a payload or not. The incubation was carried out for 48 hours in Presence of 5% FBS. The lower the value, the better is the target silencing effectiveness. The level of gene expression silencing was calculated relative to the corresponding control LNP.

[0141] Figure 10 (Fig. 10) shows the efficiency of siRNA transfection in LNPs according to the invention, more specifically expression of Target mRNA (TNC) for siRNA-LNP in U-87 MG (Glioma) Cells Compared to Empty LNPs. Incubation for 48 Hours in the Presence of 5% FBS. The lower the value, the better. The expression values comprising LNPs according to the invention as a cargo for nucleic acids are compared to control values of LNPs that do not have an active ingredient. The decimal numbers written on the x-axis represent the concentration of siRNA in the respective LNP in pg / mL for a comparison of target silencing levels in different concentrations. The target is TNC. 10A shows LNPs comprising Lipid F.

[0142] 10B shows LNPs comprising Lipid P. The expression of target mRNA (TNC) for siRNA-LNP in U-87 MG (Glioma) cells are compared to empty LNPs that comprise the same lipid composition, but do not have a payload, as control LNPs. E.g. SYV2 and SYV7 comprise the same lipid composition and were prepared at the same lipid concentration, but differ in having a payload or not. The incubation was carried out for 48 hours in the presence of 5% FBS. The lower the value, the better is the target silencing effectiveness. The level of gene expression silencing was calculated relative to the corresponding control LNP.

[0143] Figure 11 (Fig. 11, A to F) shows the expression analysis of immune response-related factors. The expression values comprising LNPs according to the invention as a cargo for nucleic acids are compared to control values of LNPs that do not have an active ingredient. The decimal numbers written on the x-axis represent the concentration of siRNA in the respective LNP in pg / mL for a comparison of gene expression levels in different concentrations. On the top row (11A to 11C) there are the values of oligoadenylate synthetase 1 (OAS1 , a factor related to the early immune response) expression, on the bottom row (11 D to 11 F) there are the values of TNC expression. 11 A and 11 D show the expression when a composition called SYV2 was used that comprised LNPs comprising siRNA and Lipid F. 11 B and 11 E show a different composition called SYV3 that comprised LNPs comprising siRNA and Lipid F. 11C and 11 F show a composition called SYV4 that comprised LNPs comprising siRNA and Lipid O. That means, e.g., 11A shows the OAS1 expression in a formulation comprising the composition called SYV2. The compositionscalled SYV7, SYV8 and SYV9 comprise LNPs without an active ingredient for comparison and represent control compositions.

[0144] Figure 12 (Fig. 12) shows the relative cell viability of the HepG2 cell line after 24 hours-incubation with 10, 20, 40, 60, 100, 200, 400, 600, 800 and 1000 pM of ionizable lipids according to the invention.

[0145] Figure 13 (Fig. 13) shows the relative cell viability of the HepG2 cell line after 48 hours-incubation with 10, 20, 40, 60, 100, 200, 400, 600, 800 and 1000 pM of ionizable lipids according to the invention.

[0146] Figure 14 (Fig. 14) shows IC50 values of ionizable lipids according to the invention plus, for better illustration, IC50 values of ionizable lipid SM-102 in comparison after 24 hours and 48 hours, respectively. The higherthe value, the better is the stability of the formulation. The better the stability of the formulation, the better can encapsulated molecules be protected.

[0147] Figure 15 (Fig. 15) shows IC50 values of HepG2 cells in minimum essential medium (MEM) in order to analyse their viability 24 hours and 48 hours after incubation with ionizable lipids according to the invention. For better illustration, IC50 values of HepG2 cells 24 hours and 48 hours after incubation with ionizable lipid SM-102 are shown in comparison.

[0148] IC50 values have been measured with ionizable lipids being present in the following concentrations: 0, 10, 20, 40, 60, 100, 200, 400, 600, 800 and 1000 pM. Presented are the average values of triplicate measurements for IC50 values along with error bars.

[0149] The higherthe value, the better is the stability of the formulation. The better the stability of the formulation, the better can encapsulated molecules be protected.

[0150] Due to the highest analysed dose of the ionizable lipids being 1000 pM, the bars in the graph do not present higher values than 1000 pM. Thus, in case of SYV-014 (48 h), SYV-015 (24 h), SYV-016 (24 h), SYV-020 (24 h), SYV-019 (24 h and 48 h), SYV-021 (24 h and 48 h), SYV-022 (24 h and 48 h), SYV-026 (24 h and 48 h) and SYV-029 (24 h and 48 h) the bars remain (artificially) at the highest measured value.This means that these presented ionizable lipids have such a low toxicity that even a dose of 1000 pM of the respective ionizable lipid does not lead to death of 50% of the HepG2 cells.

[0151] Figure 16 (Fig. 16), Figure 17 (Fig. 17) and Figure 18 (Fig. 18) show Cryo-TEM images of LNPs based on Lipid O. Further presented are size, form and morphology of the vesicles.

[0152] Figure 19 (Fig. 19), Figure 20 (Fig. 20) and Figure 21 (Fig. 21) show Cryo-TEM images of LNPs based on Lipid P. Further presented are size, form and morphology of the vesicles.

[0153] Figure 22 (Fig. 22), Figure 23 (Fig. 23) and Figure 24 (Fig. 24) show Cryo-TEM images of LNPs based on Lipid S. Further presented are size, form and morphology of the vesicles.

[0154] Definitions

[0155] The term “salt” as used herein refers to a chemical compound that consisting of cations and anions, which results in a compound with no net electric charge, i.e. that it is electrically neutral. The constituent ions are held together by electrostatic forces termed ionic bonds. The component ions in a salt can be either inorganic or organic.

[0156] An “isomer” refers to a chemical compound with the same molecular formula and molecular mass as a compound to be compared, but which differs in the linkage or spatial arrangement of the atoms. Preferably, the term “isomer” as used herein refers to a stereoisomer, such as a configuration isomer or a conformational isomer. A configuration isomer may be an enantiomer or a diastereomer, such as such as cis-trans-isomer, epimer, meso-form, endo-exo-isomer. A configuration isomer may be a rotamer or an atropisomer.

[0157] The term “alkyl” or “alkyl group” as used herein refers to a part of a molecule consisting of carbon and hydrogen atoms bonded together. The shortest possible alkyl is a methyl or methyl group. Preferably the term “alkyl” as used herein refers to a part of a molecule consisting of saturated hydrocarbons. A part of a molecule with more than one hydrocarbon may be defined herein as “alkyl chain”. An alkyl chain can act as an electron donor due to its +l effect, which may have an effect on the lipophilia of a molecule. Alkyls are often part of a lipid or a lipophilic molecule structure.

[0158] The term “alkenyl” or “alkenyl group” or “alkenyl chain” as used herein refers to a part of a molecule consisting of carbon and hydrogen atoms bonded together with one or moredouble bonds. An alkenyl is an unsaturated part of a molecule, wherein double bonds can be located at any position. There are aliphatic and cyclic alkenyl chains. The shortest possible alkenyl is ethylene or ethylene group. An alkenyl according to the invention includes its isomers, especially its cis-trans isomers. An alkenyl chain may have an effect on the lipophilia of a molecule and is often part of a lipid or a lipophilic molecule structure.

[0159] The term “conjugated alkenyl” as used herein refers to a hydrocarbon molecule with at least two double bonds, wherein two double bonds are separated by exactly one single bond. In this system, overlapping p orbitals (IT system) are present in which electrons are delocalized.

[0160] The term “alkinyl” or “alkinyl group” or “alkinyl chain” or “alkyne group” or “alkyne chain” as used herein refers to a part of a molecule consisting of carbon and hydrogen atoms bonded together with one or more triple bonds. An alkinyl is an unsaturated part of a molecule, wherein triple bonds can be located at any position. There are aliphatic and cyclic alkinyl chains. The shortest possible alkinyl is ethyne or ethyne group. An alkinyl according to the invention includes its isomers, especially its cis-trans isomers.

[0161] The term “branched” as used herein refers to a part of a molecule consisting of carbon and hydrogen atoms and has at least one side chain. A branched hydrocarbon chain has at least one carbon atom that is bonded to three or more other carbon atoms. A branched hydrocarbon can be chiral if it has a stereocenter, i.e. a carbon atom connected to four different groups. The branching also influences the van der Waals forces that act between the molecules. The longer and straighter the chain, the stronger are the forces of attraction. The shorter and more branched the chain, the weaker are the forces of attraction.

[0162] The term “unbranched” as used herein refers to a part of a molecule consisting of carbon and hydrogen atoms without a side chain.

[0163] The term “saturated” as used herein refers to a part of a molecule consisting exclusively of single bonds. Saturated hydrocarbons consist exclusively of C-C single bonds. All other possible bonds are already occupied by hydrogen atoms. With more than three carbon atoms, the part of the molecule can be unbranched or branched. Saturated parts of molecules are typical for alkyls.

[0164] The term “unsaturated” as used herein refers to a part of a molecule containing at least one double or triple bond that can be located at any position. Unsaturated parts of moleculesare typical for alkenyls and alkinyls. Unsaturated hydrocarbons are generally more reactive than saturated hydrocarbons with the same number of carbon atoms.

[0165] The term “symmetric” as used herein refers to a hydrocarbon chain which consists of the same number of carbon atoms in comparison to another hydrocarbon chain. As a nonlimiting example, R1 and R2 as used herein can be symmetric alkyls, if they have the same number of carbon atoms and thus can be hydrocarbon chains of equal length.

[0166] The term “asymmetric” as used herein refers to a hydrocarbon chain which consists of a different number of carbon atoms in comparison to another hydrocarbon chain. As a nonlimiting example, R1 and R2 as used herein can be asymmetric alkyls, if they have a different number of carbon atoms and thus can be hydrocarbon chains of different length.

[0167] The term “ionizable” as used herein refers to the capability of a chemical compound, atom or molecule to get a positive charge or a negative charge. Herein a positive charge is preferred. Removing one or more electrons of an atom or a molecule leads to a cation, which is positively charged. Attachment of an electron to a neutral atom or molecule leads to an anion, which is negatively charged. Ejection of the nucleus of an atom from the electron shell can also lead to a charged ion.

[0168] The term “lipid” as used herein refers to a compound that preferably dissolves in fats and oils than in water or can itself dissolve fats and oils better than water. A lipid as used herein has a lipophilic chemical structure. Preferably, a lipid as used herein is part of the LIPID MAPS® Structure Database (LMSD) by the LIPID MAPS Consortium.

[0169] The term “ionizable lipid” as used herein refers to a compound with lipophilic chemical structure, which is ionizable.

[0170] The term “derivative” as used herein refers to a chemical compound derived from a base substance, i.e. starting material or raw material, by replacing one or more atoms or groups of atoms with others, while retaining the basic structure. The basic structure of a derivative is equal to its base substance. Compared to its base substance, preferably (an) individual functional group(s) is / are replaced in a derivative. E.g., a benzoic acid amide is a derivative of its base substance benzoic acid.

[0171] The term “ionizable lipid nanoparticle” or “ionizable LNP” or “iLNP” as used herein refers to a nanoparticle comprising an ionizable lipid. An ionizable LNP can comprise further lipidcomponents. It may include at least another ionizable lipid, PEGylated lipids, phospholipids, structural lipids and other lipids, such as SORT lipids.

[0172] The term “phospholipid” as used herein refers to a lipid comprising at least one phosphate moiety and at least one carbon chain, such as an unsaturated fatty acid chain. Phospholipids may have a quaternized amine headgroup and a lipophilic tail group. They may help promoting fusion with the target cell and possibly with endosomes. Phospholipids can increase the phase-transition temperature and form lipid bilayer structures of iLNPs.

[0173] The term “hydrophilic” as used herein refers to a molecule or a part of a molecule that interacts preferably with water or other polar substances than with non-polar substances and tends to solvate in water.

[0174] The term “lipophilic” as used herein refers to a molecule or a part of a molecule that preferably dissolves in fats and oils than in water or can itself dissolve fats and oils better than water.

[0175] The term “PEGylated” as used herein refers to a chemical residue of a molecule comprising a polyethylene glycol group. The term “PEGylated lipid” or “polyethylene glycol lipid” as used herein refers to a lipid comprising a polyethylene glycol group. PEGylated lipids generally improve the hydrophilicity of iLNPs and thus also colloidal stability, stabilize the structures of iLNPs, prevents nanoparticles aggregation, avoid rapid clearance of the molecule to be delivered by the target organism, and increase circulation time in vivo and reduce clearance.

[0176] The term “structure lipid” or “structural lipid” as used herein refers to lipids with a membrane fusion function. They are made to promote the uptake of molecules, such as mRNA, into cytoplasm and to enhance nanoparticle stability. Cholesterol and sitosterol are examples for lipids with the function of a structure lipid.

[0177] The term “SORT lipid” or “Selective organ targeting lipid” as used herein refers to mostly phospholipids with charge, including permanent cationic lipids, negatively charged lipids, and other ionizable lipids. SORT lipids may affect the in vivo distribution.

[0178] When a part of a molecule is “connected to” another part of a molecule or a chemical residue as used herein, a chemical bonding is described. The sort of chemical bonding includes covalent bonds, ionic bonds, metallic bonds, hydrogen bonds and Van der Waalsinteractions as well as connecting moieties. E.g., when a molecule or a part of a molecule is connected to another molecule or part of a molecule via an alkyl, the alkyl is the connecting moiety that connects the molecules or molecule parts.

[0179] The term “pharmaceutically acceptable” is used herein to refer to those compounds, materials, compositions, and / or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, allergic response, irritation, or other problem or complication, commensurate with a reasonable benefit-risk ratio.

[0180] The term “tail group” as used herein refers to a chemical part of the molecule which can be considered the lipophilic part of the molecule. Usually the tail group is a hydrocarbon chain, preferably an alkyl or alkenyl.

[0181] The term “head group” as used herein refers to a chemical part of the molecule which can be considered ionizable. It may comprise a hetero atom, preferably an ionizable nitrogen atom.

[0182] The term “core” as used herein refers to a chemical moiety which connects the head group to the tail group of a molecule.

[0183] The term “patient” as used herein refers to a subject who may seek or be in need of treatment, requires treatment, is receiving treatment, will receive treatment, or a subject who is under care by a trained professional for a particular disease or condition.

[0184] The term “PC” as used herein refers to phosphatidylcholine. The term “GMO” as used herein refers to a genetically modified organism. The term “NON-GMO” as used herein refers to an organism that is not genetically modified. The term “DSPC” as used herein refers to 1 ,2-distearoyl-sn-glycero-3-phosphocholine. The term “DPPC” as used herein refers to 1 ,2-dipalmitoyl-sn-glycero-3-phosphocholine. The term “HSPC” as used herein refers to hydrogenated soybean phosphatidylcholine. The term “HEPC” as used herein refers to hydrogenated egg yolk phosphatidylcholine. The term “DLPC” as used herein refers to 1 ,2-dilinoleoyl-sn-glycero-3-phosphocholine. The term “DMPC” as used herein refers to 1 ,2-dimyristoyl-sn-glycero-phosphocholine. The term “DOPC” as used herein refers to 1 ,2-dioleoyl-sn-glycero-3-phosphocholine. The term “DUPC” as used herein refers to 1 ,2-diundecanoyl-sn-glycero-phosphocholine. The term “POPC” as used herein refers to 1-palmitoy 1-2-oleoy 1-sn-glycero-3-phosphocholine. The term “SOPC” as used hereinrefers to 1 -stearoyl-2-oleoylphosphatidylcholine. The term “ePC” as used herein refers to egg yolk phosphatidylcholine. The term “sPC” as used herein refers to soybean phosphatidylcholine. The term “hPC” as used herein refers to sunflower phosphatidylcholine. The term “PE” as used herein refers to phosphatidylethanolamine. The term “DOPE” as used herein refers to 1 ,2-dioleoyl-sn-glycero-3-phosphoethanolamine. The term “POPE” as used herein refers to palmitoyloleoylphosphatidylethanolamine. The term “DPPE” as used herein refers to dipalmitoylphosphatidylethanolamine. The term “DMPE” as used herein refers to dimyristoylphosphoethanolamine. The term “SOPE” as used herein refers to 1-stearoyl-2-oleoyl-phosphatidyethanolamine. The term “LPE” as used herein refers to lysophosphatidylethanolamine. The term “PG” as used herein refers to phosphatidylglycerol. The term “DSPG” as used herein refers to 1 ,2-Distearoyl-sn-glycero-3-phosphoglycerol. The term “DOPG” as used herein refers to 1 ,2-dioleoyl-sn-glycero-3-phospho-1 -glycerol. The term “DPPG” as used herein refers to dipalmitoylphosphatidylglycerol. The term “PA” as used herein refers to phosphatidic acid. The term “DPPA” as used herein refers to 1 ,2-Dipalmitoyl-sn-glycero-3-phosphatidic acid. The term “PI” as used herein refers to phosphatidylinositol. The term “PS” as used herein refers to phosphatidylserine. The term “DSPS” as used herein refers to 1 ,2-Distearoyl-sn-glycero-3-phospho-L-serine. The term “LPL” as used herein refers to monoacyl phospholipids such as lysophospholipid.

[0185] The term “DMG-PEG” as used herein refers to 1 ,2-dimyristoyl-sn-glycerol methoxypolyethyleneglycol. The term “DSPE-PEG” as used herein refers to 1 ,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)]. The term “DSG-PEG” as used herein refers to disteryl glycerol polyethyleneglycol. The term “PEG-CER” as used herein refers to PEGylated ceramide. The term “PEG-DEG” as used herein refers to PEGylated diacylglycerol. The term “PEG-DMPE” as used herein refers to PEGylated dimyristoylphosphoethanolamine. The term “PEG-DPPC” as used herein refers to PEGylated DPPC. The term “PEG-c-DOMG” as used herein refers to [(Methoxy-poly(ethyleneglycol)2000)carbamoyl]-1 ,2-dimyristyloxlpropyl-3-amine. The term “DPPE-PEG” as used herein refers to PEGylated DPPE. The term “c-DMA-PEG” as used herein refers to PEGylated 1 ,2-dimyristoyl-sn-glycerol. The term “pSar” as used herein refers to polysarcosine. The term “DMG-pSar25” as used herein refers to 1 ,2-dimyristoyl-sn-glycero-3-succinyl-N-polysarcosine-25. The term “DOPE-pSar” as used herein refers to 1 ,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-polysarcosine-25.

[0186] The term “DODAP” as used herein refers to 1 ,2-dioleoyl-3-dimethylammonium-propane. The term “DOTAP” as used herein refers to 1 ,2-dioleoyl-3-trimethylammonium-propane.The term “DPDAB” as used herein refers to 1 ,2-dipalmitoyl-3-dimethylammonium-propane. The term “DODMA” as used herein refers to 1 ,2-dioleyloxy-3-dimethylaminopropane. The term “MPA” as used herein refers to 1 ,2-dimyristoyl-sn-glycero-3-phosphate. The term “18BMP” as used herein refers to bis(monooleoylglycero)phosphate. The term “18PA” as used herein refers to 1 ,2-dioleoyl-sn-glycero-3-phosphate. The term “DC-cholesterol” as used herein refers to dimethylaminoethane-carbamoyl-cholesterol. The term “5A2-SC8” as used herein refers to a compound defined by CAS number 1857341-90-2.

[0187] The term “MC3” as used herein refers to the lipid D-Lin-MC3-DMA. The term “C12” as used herein refers to the lipid C12-200.

[0188] The term “post-encapsulation” as used herein refers to a method to encapsulate an active ingredient into LNPs by incubation of the active ingredient with preformed LNPs. Preferably, a RNA solution is incubated with preformed RNA-free LNPs to prepare the RNA-LNPs. Particularly preferably, a mRNA solution is incubated with preformed mRNA-free LNPs to prepare the mRNA-LNPs.

[0189] Detailed description of the invention

[0190] The present invention provides novel compounds suitable as ionizable lipids, even representing a novel class of ionizable lipids. It further provides ionizable lipid nanoparticles and compositions related thereto and uses thereof. The key contribution of the invention is a ionizable lipid whose chemical structure is based on a benzene core with oxygen residues, especially being represented by an ester or ether group, wherein a tertiary amine is connected to one of said oxygen residues via an alkyl group. In particular, the benzene core with oxygen residues is represented by a hydroxybenzoic acid structure or a hydroxyhydroquinone structure, which are exceptionally effective for the formation of LNPs used in molecule delivery. The core moiety may have chemical residues in ortho-, meta-and / or para-position which offers different ionisation potentials. The lipids according to the invention are moreover characterised by the presence of specific alkyl chains connected to a carboxyl group as part of the hydroxybenzoic acid, or to a carbon atom connecting both of the vicinal oxygen residues of the hydroxyhydroquinone, to increase the hydrophobicity of the lipid and the stability of the resulting. A further main contribution is a tertiary amine group which is evident for the capability of being ionized.

[0191] The present invention provides completely new chemical structural classes of compounds suitable as ionizable lipids and thus expands the possibilities in the field of LNP technologytremendously. By efficiently protecting and delivering molecules to specific locations of various target organism, bioavailability can be enhanced, while the biodegradable compounds lead to lower toxicity for the respective target organism. A wide range of uses of such compounds, ionizable lipids, LNPs and compositions according to the invention is the result.

[0192] To this end, the present invention provides, in a first aspect, a compound being represented by formula (A) or formula (B) or formula (C) or a salt or stereoisomer thereof, preferably being suitable as lipid, particularly preferably being used as ionizable lipid

[0193]

[0194] formula (A),

[0195] wherein n is 1 , 2, 3, 4, 5 or 6, preferably 1 , 2, 3 or 4, more preferably 2 or 3, and

[0196] wherein R1 is an alkyl, a conjugated alkenyl, or an alkinyl, and

[0197] wherein R2 is selected from the group consisting of H, COOH, benzyl, phenol, an alkyl, and a conjugated alkenyl,

[0198] wherein R3 and R4 are independently selected from the group consisting of H, NH2, benzyl, phenol, benzoic acid, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, an alkyl, and an alkenyl, and

[0199] wherein R5 is selected from the group consisting of H, NH2, an alkyl, an alkenyl or an alkinyl, or

[0200]

[0201] formula (B),

[0202] wherein Re is represented by formula (B-1)

[0203]

[0204] formula (B-1),

[0205] or a salt or stereoisomer thereof, and

[0206] wherein m is 1 , 2, 3, 4, 5 or 6, preferably 2, 3, 4 or 5, particularly preferably 2 or 5, and

[0207] wherein R? is represented by formula (B-1) or a salt or stereoisomer thereof, or is selected from the group consisting of H, an alkyl with a total number of carbon atoms in the range from 1 to 7, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group, and

[0208] wherein Rs is represented by formula (B-1) or a salt or stereoisomer thereof, or is selected from the group consisting of H, an alkyl with a total number of carbon atoms in the range from 1 to 7, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group or a propanol group, and

[0209] wherein Rg is selected from the group consisting of H, O-RBI or an alkyl,

[0210] wherein RBI is H or an alkyl, and,when RBI is an alkyl, RBI has a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14 or 15, and optionally comprises one or more hetero atoms as chemical residue, preferably wherein Rg comprises a sole ether group being O-RBI as defined in formula (B-1), and

[0211] wherein Rio is selected from the group consisting of H, O-RB2 or an alkyl,

[0212] wherein RB2 is H or an alkyl, and,

[0213] optionally when RB2 is an alkyl, RB2 comprises one or more hetero atoms as chemical residue, preferably wherein Rio comprises a sole ether group being O-RB2 as defined in formula (B-1), and

[0214] wherein Rn is selected from the group consisting of H, O-RB3 or an alkyl,

[0215] wherein RB3 is H or an alkyl, and,

[0216] when RB3 is an alkyl, RB3 has a total number of carbon atoms of 1 , 2, 3 or 4 and / or wherein m is 5 and / or wherein Rio is O-RB2, and

[0217] when Rio is O-RB2, RB2 is an alkyl with a total number of carbon atoms of 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, and optionally comprises one or more hetero atoms as chemical residue, wherein Rn comprises a sole ether group being O-RB3 as defined in formula (B-1), and

[0218] wherein R12 is selected from the group consisting of H, O-RB4 or an alkyl,

[0219] wherein RB4 is H or an alkyl, and

[0220] optionally when RB4 is an alkyl, RB4 comprises one or more hetero atoms as chemical residue, preferably wherein R12 comprises a sole ether group being O-RB4 as defined in formula (B-1), and

[0221] preferably wherein at least one of R9, R10, R11 or R12 is selected from the group consisting of O-RBI, O-RB2, O-RB3 or RB4,

[0222]

[0223] formula (C),

[0224] wherein k is 1 , 2, 3, 4, 5 or 6, preferably 2, 3, 4 or 5, particularly preferably 2 or 3, and wherein R13 is an alkyl, an alkenyl or an alkinyl, preferably wherein the alkenyl is a conjugated alkenyl, more preferably wherein R13 is an alkyl, and wherein RM is selected from the group consisting of H, a benzyl, an alkyl or an alkenyl, preferably an alkyl, and wherein R15 is selected from the group consisting of H, a methanol group, an ethanol group, a propanol group, a butanol group, a pentanol group or an alkyl, preferably an alkyl, more preferably an alkyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, or above, particularly preferably an alkyl with a total number of carbon atoms of 4 or 5, and wherein R16 is selected from the group consisting of H, an ethanol group, a propanol group, a butanol group, a pentanol group or an alkyl, preferably an alkyl, more preferably an alkyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, or above, particularly preferably an alkyl with a total number of carbon atoms of 4 or 5, and preferably wherein R15 and R16 are bond together via an alkyl group to represent a cyclic structure, more preferably to represent a pyrrolidine, a piperidine, a pyrrole or a pyridine, particularly preferably a pyrrolidine or piperidine.

[0225] In one embodiment the alkyl or conjugated alkenyl or alkinyl representing R1 may have a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above.

[0226] In a preferred embodiment, R1 may be an alkyl with a total number of carbon atoms in the range from 4 to 17, more preferably an alkyl with a total number of carbon atoms in the range from 8 to 15, particularly preferably an alkyl with a total number of carbon atoms in the range from 10 to 13.

[0227] In one embodiment, R2 may be H. In another embodiment, R2 may be an alkyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, preferably an alkyl with a total number of carbon atoms in the range from 4 to 17, more preferably an alkyl with a total number of carbon atoms in therange from 8 to 15, particularly preferably an alkyl with a total number of carbon atoms in the range from 9 to 13.

[0228] In yet another embodiment, R2 may be a conjugated alkenyl with a total number of carbon atoms in the range from 1 to 20.

[0229] In one embodiment, R3 may be an alkyl with a total number of carbon atoms in the range from 1 to 7, preferably an alkyl with a total number of 1 , 2, 3, 4 or 5 carbon atoms, more preferably an alkyl with a total number of 1 or 4 carbon atoms, particularly preferably a methyl group.

[0230] In another embodiment, R3 may be an alkenyl with a total number of carbon atoms in the range from 1 to 10.

[0231] In one embodiment, R4 may be an alkyl with a total number of carbon atoms in the range from 1 to 7, preferably an alkyl with a total number of 1 , 2, 3, 4 or 5 carbon atoms, more preferably an alkyl with a total number of 1 or 4 carbon atoms, particularly preferably a methyl group.

[0232] In another embodiment R4 may be an alkenyl with a total number of carbon atoms in the range from 1 to 10.

[0233] In one embodiment, the alkyl representing R3 can be a cyclic structure to connect R3 and R4.

[0234] In one embodiment, R3 and R4 can be connected to the tertiary amine to represent a pyrrolidine. In another embodiment, R3 and R4 can be connected to the tertiary amine to represent a piperidine. In yet another embodiment, R3 and R4 can be connected to the tertiary amine to represent a pyrrole. In a further embodiment, R3 and R4 can be connected to the tertiary amine to represent a pyridine.

[0235] In another embodiment, the alkenyl representing R3 can be a cyclic structure to connect R3 and R4.

[0236] In one embodiment, R5 may be H. In another embodiment, R5 may be an alkyl with a total number of carbon atoms in the range from 1 to 25, preferably an alkyl with a total number of carbon atoms in the range from 10 to 19, more preferably an alkyl with a total number ofcarbon atoms in the range from 12 to 18, particularly preferably an alkyl with a total number of 17 carbon atoms.

[0237] In yet another embodiment, Ra may be an alkenyl with a total number of carbon atoms in the range from 1 to 25. In a further embodiment, Ra may be an alkinyl with a total number of carbon atoms in the range from 1 to 25.

[0238] According to the present disclosure, R1, R2, R3, R4 and R5 may be individually selected according to the embodiments detailed above, unless specific combinations are individually provided.

[0239] In one embodiment, R7 may be represented by formula (B-1). In another embodiment, R7 may be an alkyl with a total number of carbon atoms in the range from 1 to 7, preferably a methyl group.

[0240] In yet another embodiment, R7 may be an alkenyl with a total number of carbon atoms in the range from 1 to 7.

[0241] In one embodiment, the alkyl representing R7 can be a cyclic structure to connect R7 and Ra. Thus, a cyclic tertiary amine can be represented herein.

[0242] In another embodiment, the alkenyl representing R7 can be a cyclic structure to connect R7 and Ra. Thus, an aromatic tertiary amine can be represented herein.

[0243] In one embodiment, Ra may be represented by formula (B-1). In another embodiment Ra may be an alkyl with a total number of carbon atoms in the range from 1 to 7, preferably a methyl group or a propanol group.

[0244] In yet another embodiment, Ra may be an alkenyl with a total number of carbon atoms in the range from 1 to 7.

[0245] In one embodiment, the alkyl representing Ra can be a cyclic structure to connect R7 and Ra. Thus, a cyclic tertiary amine can be represented herein.

[0246] In another embodiment, the alkenyl representing Ra can be a cyclic structure to connect R7 and Ra. Thus, an aromatic tertiary amine can be represented herein.According to the present disclosure, Re, R? and Re may be individually selected according to the embodiments detailed above, unless specific combinations are individually provided.

[0247] In one embodiment, Rg may be H. In another embodiment, Rg may be O-RBI.

[0248] In one embodiment, RBI may be H. In another embodiment, RBI may be an alkyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above. In a preferred embodiment, RBI may be an alkyl with a total number of carbon atoms in the range from 1 to 15, more preferably an alkyl with a total number of carbon atoms in the range from 10 to 12 carbon atoms.

[0249] In one embodiment, RBI may be an alkyl comprising one or more hetero atoms as chemical residue, preferably wherein Rg comprises a sole ether group being O-RBI as defined in formula (B-1).

[0250] In one embodiment, Rio may be H. In another embodiment, Rio may be O-RB2.

[0251] In one embodiment, RB2 may be H. In another embodiment, RB2 may be an alkyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above. In a preferred embodiment, RB2 may be an alkyl with a total number of carbon atoms in the range from 10 to 20, more preferably an alkyl with a total number of carbon atoms in the range from 12 to 16, particularly preferably an alkyl with a total number of 12 or 16 carbon atoms.

[0252] In one embodiment, RB2 may be an alkyl comprising one or more hetero atoms as chemical residue, preferably wherein Rio comprises a sole ether group being O-RB2 as defined in formula (B-1).

[0253] In one embodiment, Rn may be H. In another embodiment, Rn may be O-RB2.ln yet another embodiment, Rn may be an alkyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above. In a preferred embodiment, Rn may be an alkyl with a total number of carbon atoms in the range from 10 to 20, preferably an alkyl with a total number of carbon atoms in the range from 15 to 18, particularly preferably an alkyl with a total number of 15 or 18 carbon atoms.

[0254] In one embodiment, RB3 may be H. In another embodiment, RB3 may be an alkyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19,20, 21 , 22, 23, 24, 25, or above. In a preferred embodiment, RB3 may be an alkyl with a total number of carbon atoms in the range from 10 to 20, more preferably an alkyl with a total number of carbon atoms in the range from 15 to 18, particularly preferably an alkyl with a total number of 15 or 16 carbon atoms or an alkyl with a total number of 1 , 2, 3 or 4 carbon atoms.

[0255] In yet another embodiment, RB3 may be an alkyl, wherein m is 5.

[0256] In a further embodiment, RB3 may be an alkyl and Rio may be O-RB2, wherein RB2 is an alkyl with a total number of carbon atoms of 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above.

[0257] In one embodiment, RB3 may be an alkyl comprising one or more hetero atoms as chemical residue, wherein Rn comprises a sole ether group being O-RB3 as defined in formula (B-1).

[0258] In one embodiment, R12 may be H. In another embodiment, R12 may be O-RB4.

[0259] In one embodiment, RB4 may be H. In another embodiment, RB4 may be an alkyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above. In a preferred embodiment, RB4 may be an alkyl with a total number of carbon atoms in the range from 10 to 20, more preferably an alkyl with a total number of carbon atoms in the range from 12 to 16, particularly preferably an alkyl with a total number of 12 or 16 carbon atoms.

[0260] In one embodiment, RB4 may be an alkyl comprising one or more hetero atoms as chemical residue, preferably wherein R12 comprises a sole ether group being O-RB4 as defined in formula (B-1).

[0261] According to the present disclosure, R9, R10, R11 and R12 may be individually selected according to the embodiments detailed above, unless specific combinations are individually provided.

[0262] In one embodiment, the alkyl or alkenyl or alkinyl representing R13 may have a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above.In a preferred embodiment, R13 may be an alkyl with a total number of carbon atoms in the range from 4 to 17, more preferably an alkyl with a total number of carbon atoms in the range from 8 to 15, particularly preferably an alkyl with a total number of 13 carbon atoms. In another embodiment, R13 may be a conjugated alkenyl.

[0263] In one embodiment, RM may be H. In another embodiment RM may be a benzyl.

[0264] In a preferred embodiment, R1 may be an alkyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, preferably an alkyl with a total number of carbon atoms in the range from 4 to 17, more preferably an alkyl with a total number of carbon atoms in the range from 8 to 15, particularly preferably an alkyl with a total number of 13 carbon atoms.

[0265] In another embodiment, R1 may be an alkenyl with a total number of carbon atoms in the range from 1 to 20. In yet another embodiment, R1 may be a conjugated alkenyl.

[0266] In one embodiment, R15 may be H. In another embodiment, R15 may be a methanol. In yet another embodiment, R15 may be an ethanol. In a further embodiment, R15 may be a propanol. In still another embodiment, R15 may be a butanol. In an even further embodiment, R15 may be a pentanol.

[0267] In a preferred embodiment, R15 may be an alkyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, or above, preferably an alkyl with a total number of carbon atoms of 4 or 5, particularly preferably a butyl group.

[0268] In another embodiment, R15 may be an alkenyl with a total number of carbon atoms in the range from 1 to 10.

[0269] In one embodiment, R16 may be H. In another embodiment, R16 may be a methanol. In yet another embodiment, R16 may be an ethanol. In a further embodiment, R16 may be a propanol. In still another embodiment, R16 may be a butanol. In an even further embodiment, R16 may be a pentanol.

[0270] In a preferred embodiment, R16 may be an alkyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, or above, preferably an alkyl with a total number of carbon atoms of 4 or 5, particularly preferably a butyl group.In another embodiment Ri6 may be an alkenyl with a total number of carbon atoms in the range from 1 to 10.

[0271] In one embodiment, R15 and R16 are bond together via an alkyl group to represent a cyclic structure.

[0272] In one embodiment, R15 and R16 can be connected to the tertiary amine to represent a pyrrolidine. In another embodiment, R15 and R16 can be connected to the tertiary amine to represent a piperidine. In yet another embodiment, R15 and R16 can be connected to the tertiary amine to represent a pyrrole. In a further embodiment, R15 and R16 can be connected to the tertiary amine to represent a pyridine.

[0273] In another embodiment, the alkenyl representing R15 can be a cyclic structure to connect R15 and R16.

[0274] It was advantageously found that the lipid chains represented by R1 , R2, R3, R R5, R9, R10, R11, R12, RBI, RB2, RB3, RB4, R15 and R16, especially R1, R2, R5, R9, R10, R11 , R12, RBI, RB2, RB3, RB4, R^and RBI6, are critical to the stability of the resulting compounds, ionizable lipids and / or LNPs. They may have a certain chain length to increase the hydrophobicity of the lipid. Moreover, these tail groups may be characterised by the presence of specific alkyl chains, alkenyl chains or alkinyl chains, preferably alkyl chains, that are connected to a carboxyl group, preferably to the oxygen atom of an ester group, or to a carbon atom connecting two oxygen atoms in positions 1 and 2 of a hydroxyhydroquinone structure according to IUPAC nomenclature, which represent a feature of a completely novel class of ionizable lipids or compounds being suitable therefor.

[0275] In a preferred embodiment, there is provided a compound according to the various aspects, wherein the tertiary amine being represented as N in formula (A) or formula (B) or formula (C) may be a tertiary aliphatic amine. In another embodiment, there is provided a compound according to the various aspects, wherein the tertiary amine being represented as N in formula (A) or formula (B) or formula (C) may be a tertiary cyclic amine. In one embodiment the tertiary cyclic amine may be represented by a pyrrolidine. In another embodiment the tertiary cyclic amine may be represented by a piperidine. In yet another embodiment, there is provided a compound according to the various aspects, wherein the tertiary amine being represented as N in formula (A) or formula (B) or formula (C) may be a tertiary aromatic amine. A tertiary amine group is evident for the capability of being ionized. The differentembodiments may have an effect on the basic quantity of the tertiary amine and thus be ionized in different circumstances.

[0276] In another embodiment, there is provided a compound according to the various aspects, wherein further at least one of Ri, R2, R5, R9, R10, R11 and R12 is / are an alkyl, alkenyl or an alkinyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, preferably with a total number of carbon atoms in the range from 6 to 24, more preferably wherein at least one of R1, R2, R5, R9, R10, R11 and R12 has a total number of carbon atoms of 10, 12, 13, 15, 16, 17 or 18.

[0277] In one embodiment, the alkenyl representing at least one of R1 and R2 is a conjugated alkenyl. In one embodiment, the conjugated alkenyl representing at least one of R1 and R2 has a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above.

[0278] In another embodiment, at least one of RBI, RB2, RB3 and RB4 is / are an alkyl.

[0279] In one embodiment, the alkyl representing at least one of R1, R2, Rs, R9, R10, R11, R12, R13, R14, RBI, RB2, RB3 and RB4 is branched. In another embodiment, the alkyl representing at least one of R1, R2, Rs, R9, R10, R11, R12, R13, R14, RBI, RB2, RB3 and RB4 is unbranched.

[0280] In one embodiment, the alkenyl representing at least one of R1, R2, Rs, R9, R10, R11 , R12, R13 or R14 is branched. In another embodiment, the alkenyl representing at least one of R1, R2, Rs, R9, R10, R11, R12, R13 or R14 is unbranched.

[0281] In one embodiment, the alkinyl representing at least one of R1, R2, Rs, R9, R10, R11 , R12, R13 or R14 is branched. In another embodiment, the alkinyl representing at least one of R1, R2, Rs, R9, R10, R11, R12, R13 or R14 is unbranched.

[0282] In one embodiment, the alkenyl representing at least one of R1, R2, Rs, R9, R10, R11 , R12, R13 or R14 is saturated. In another embodiment, the alkenyl representing at least one of R1, R2, Rs, R9, R10, R11, R12, R13, R14 is unsaturated.

[0283] In one embodiment, the alkinyl representing at least one of R1, R2, Rs, R9, R10, R11 , R12, R13 or R14 is saturated. In another embodiment, the alkinyl representing at least one of R1, R2, Rs, R9, R10, R11, R12, R13 or R14 is unsaturated.In one embodiment, the alkyl representing at least one of R-i, R2, R5, R9, R10, R11, R12, R13, R14, RBI, RB2, RB3 and RB is symmetric. In another embodiment, the alkyl representing at least one of R1, R2, R5, R9, R10, R11, R12, R13, R14, RBI, RB2, RB3 and RB is asymmetric.

[0284] In one embodiment, the alkenyl representing at least one of R1, R2, R5, R9, R10, R11 , R12, R13 or R14 is symmetric. In another embodiment, the alkenyl representing at least one of R1, R2, R5, R9, R10, R11, R12, R13 or R14 is asymmetric.

[0285] In one embodiment, the alkinyl representing at least one of R1, R2, R5, R9, R10, R11 , R12, R13 or R14 is symmetric. In another embodiment, the alkinyl representing at least one of R1, R2, R5, R9, R10, R11, R12, R13 or R14 is asymmetric.

[0286] In yet another embodiment, there is provided a compound according to the various aspects, wherein further the alkyl representing at least one of R1, R2, R5, R9, R10, R11, R12, R13, R14, RBI, RB2, RB3 and RB can comprise one or more hetero atoms as chemical residue. In a preferred embodiment the hetero atom(s) is / are oxygen atom(s). In a further embodiment, the hetero atom(s) is / are nitrogen atom(s). In yet a further embodiment, the hetero atom(s) is / are halogen atom(s), selected from a group consisting of F, Cl, Br, I and At.

[0287] In yet another embodiment, there is provided a compound according to the various aspects, wherein further the alkenyl representing at least one of R1, R2, R5, R9, R10, R11, R12, R13 or R14 can comprise one or more hetero atoms as chemical residue. In a preferred embodiment the hetero atom(s) is / are oxygen atom(s). In a further embodiment, the hetero atom(s) is / are nitrogen atom(s). In yet a further embodiment, the hetero atom(s) is / are halogen atom(s), selected from a group consisting of F, Cl, Br, I and At.

[0288] In yet another embodiment, there is provided a compound according to the various aspects, wherein furtherthe alkinyl representing at least one of R1, R2, R5, R9, R10, R11, R12, R13 or R14 can comprise one or more hetero atoms as chemical residue. In a preferred embodiment the hetero atom(s) is / are oxygen atom(s). In a further embodiment, the hetero atom(s) is / are nitrogen atom(s). In yet a further embodiment, the hetero atom(s) is / are halogen atom(s), selected from a group consisting of F, Cl, Br, I and At.

[0289] In one embodiment, R9 comprises a sole ether group being O-RBI as defined in formula (B-1). In one embodiment, R10 comprises a sole ether group being O-RB2 as defined in formula (B-1). In one embodiment, Rn comprises a sole ether group being O-RB3 as defined informula (B-1). In one embodiment, R12 comprises a sole ether group being O-RB4 as defined in formula (B-1).

[0290] In a further embodiment, there is provided a compound according to the various aspects being represented by formula (1), (2), (3), (4), (5), (6), (7), (8), (9), (10), (11), (12), (13), (14), (15), (16), (17), (18), (19), (20), (21), (22), (23), (24), (25), (26) or (27) or a salt or stereoisomer thereof, preferably being suitable as lipid, particularly preferably being used as ionizable lipid

[0291]

[0292] formula (3),

[0293]

[0294] formula (4),

[0295]

[0296] formula (8),

[0297]

[0298] formula (9),

[0299]

[0300] formula (10),

[0301]

[0302] formula (11),

[0303]

[0304] formula (14),

[0305]

[0306] formula (17),

[0307]

[0308] formula (21),

[0309]

[0310] formula (25),

[0311]

[0312] formula (27).

[0313] Surprisingly it was found that the compounds according to the invention are able to reduce toxicity for the target organism, as it can be seen in Fig. 4, Fig. 12, Fig. 13, Fig 14 and Fig. 15.

[0314] The compounds according to the invention, may be suitable as autonomous main ingredient. Preferably, they can be a carrier or an excipient.

[0315] Advantageously the compounds being suitable as ionizable lipids can increase the stability of LNP formulations and thus protect the main ingredient and the formulation itself. This is a key contribution to deliver molecules to a specific location of a target organism, as it can be seen in Fig 1 , Fig. 2 and Fig. 3.

[0316] Further, there was surprisingly found the compounds being suitable as ionizable lipid being highly bioavailable and easily tissue compatible. Therefore, they can be used effectively in several fields of operations, examples can be seen in Fig. 5, Fig. 6, Fig. 7 and Fig. 11. Apart from the use in immune modulation or drug targeting, they can be used in further application areas such as cosmetics, nutrition and the agricultural sector. The compounds according to the invention are moreover highly functional and are able to effectively deliver main ingredients to provide a desired effect, as it can be seen in Fig. 8, Fig. 9 and Fig. 10.In a second aspect, there is provided an ionizable lipid according to the various aspects, comprising a hydroxybenzoic acid structure, wherein one tertiary amine is present and wherein the tertiary amine has at least one chemical residue, wherein the chemical residue is selected from the group consisting of H, an alkyl, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group, a butyl group ora propanol group, or wherein the tertiary amine is a tertiary cyclic amine, preferably the being present as part of a pyrrolidine, a piperidine, a pyrrole or a pyridine structure, preferably a pyrrolidine or piperidine, and wherein not more than two ester groups are present, preferably wherein not more than one ester group is present, wherein the carboxyl group of the hydroxybenzoic acid has an alkyl, a conjugated alkenyl or an alkinyl as chemical residue, and wherein the tertiary amine is connected to the phenolic oxygen atom of the hydroxybenzoic acid via an alkyl group, or wherein the ionizable lipid has a chemical structure of formula (A) as defined above, or

[0317] wherein the ionizable lipid has a chemical structure of formula (B), wherein formula (B) includes formula (B-1), as defined above.

[0318] In a preferred embodiment, the alkyl group connecting the tertiary amine to the phenolic oxygen atom of the hydroxybenzoic acid has a total number of carbon atoms of 2, 4 or 5.

[0319] In a preferred embodiment, one hydroxybenzoic acid is present.

[0320] In another embodiment, two hydroxybenzoic acids are present. In yet another embodiment, three hydroxybenzoic acids are present.The core of the compound being suitable as an ionizable lipid based on a benzene core with oxygen residues is particularly effective for the formation of LNPs used in molecule delivery.

[0321] In certain embodiments the core structure is represented by a hydroxybenzene moiety, like e.g. hydroxyhydroquinone. A preferred embodiment features a hydroxybenzoic acid as core of the compound according to the invention. The core moiety may have chemical residues in ortho-, meta- and / or para-position. The invention includes variations where the hydroxyl-and carboxyl-substituents are in ortho-, meta- or para-positions on the benzene ring of the hydroxybenzoic acid core. These positional isomers offer different ionisation potentials and can be selected based on the desired release profile of the encapsulated drug.In one embodiment, the aromatic group of the hydroxybenzoic acid has H, an ether or an alkyl as a chemical residue.

[0322] In one embodiment, the tail group as chemical residue of the ether and / or the aromatic group of the hydroxybenzoic acid and / or the oxygen atom of the carboxyl group is an alkyl, an alkenyl or an alkinyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, more preferably with a total number of carbon atoms in the range from 6 to 24, particularly preferably with a total number of carbon atoms of 10, 12, 13, 15, 16, 17 or 18.

[0323] In one embodiment, there is provided an ionizable lipid according to the various aspects, wherein one tertiary amine is present and wherein the tertiary amine has at least one chemical residue, wherein the chemical residue is selected from the group consisting of H, an alkyl, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group or a propanol group.

[0324] In a preferred embodiment the tertiary amine is connected to the phenolic oxygen atom of the hydroxybenzoic acid via an alkyl group, or the tertiary amine is connected to the oxygen atom of the carbonyl group of the hydroxybenzoic acid via an alkyl group.

[0325] In a preferred embodiment the carboxyl group of the hydroxybenzoic acid is connected to the tertiary amine via an alkyl group.

[0326] In a preferred embodiment the aromatic group of the hydroxybenzoic acid has H, an ether or an alkyl as a chemical residue.

[0327] In one embodiment the tail group as chemical residue of the ether and / or the aromatic group of the hydroxybenzoic acid and / or the oxygen atom of the carboxyl group is an alkyl, an alkenyl or an alkinyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, preferably with a total number of carbon atoms in the range from 6 to 24, particularly preferably with a total number of carbon atoms of 10, 12, 13, 15, 16, 17 or 18.

[0328] In a third aspect, there is provided an ionizable lipid according to the first aspect and the various embodiments related thereto, comprising a hydroxyhydroquinone structure, preferably wherein the ionizable lipid has a chemical structure of formula (C) as defined above, wherein one tertiary amine is present and wherein the tertiary amine has at leastone chemical residue, wherein the chemical residue is selected from the group consisting of H, an alkyl, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group, a butyl group or a propanol group, or wherein the tertiary amine is a tertiary cyclic amine, preferably the being present as part of a pyrrolidine, a piperidine, a pyrrole or a pyridine structure, preferably a pyrrolidine or piperidine, and wherein the tertiary amine is connected to the oxygen atom in position 4 of the hydroxyhydroquinone structure according to IUPAC nomenclature via an alkyl group.

[0329] The core of the compound being suitable as an ionizable lipid based on a hydroxyhydroquinone is particularly effective for the formation of LNPs used in molecule delivery.

[0330] In a preferred embodiment, the two oxygen atoms in positions 1 and 2 of the hydroxyhydroquinone structure according to IUPAC nomenclature are connected via a carbon atom, more preferably wherein the connecting carbon atom has at least one alkyl with a total number of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, as chemical residue, particularly preferably with a total number of carbon atoms of 13.

[0331] In one embodiment, there is provided an ionizable lipid according to the various aspects, wherein one tertiary amine is present and wherein the tertiary amine has at least one chemical residue, wherein the chemical residue is selected from the group consisting of H, an alkyl, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group or a propanol group.

[0332] In one embodiment the tail group as chemical residue of the carbon atom that is connecting the vicinal oxygen residues of the hydroxyhydroquinone is an alkyl, an alkenyl or an alkinyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, preferably with a total number of carbon atoms in the range from 6 to 24, particularly preferably with a total number of carbon atoms of 13.

[0333] In a fourth aspect, there is provided a method of producing the compound according to the first aspect and the various embodiments related thereto, or the lipid according to the second aspect and the embodiments related thereto, or the lipid according to the third aspect and the embodiments related thereto,

[0334] wherein the method comprises the following steps, in sequence:a) providing a raw material comprising a structure of hydroxbenzoic acid or a derivative or a salt thereof or a structure of hydroxyhydroquinone or a derivative or a salt thereof,

[0335] b) mixing the provided raw material with a substance for elongating the tail group of the provided raw material,

[0336] c) adding a substance to the mixture obtained in b) for hydrating a derivative of a hydroxyl group of the mixture obtained in b),

[0337] d) adding a substance comprising a tertiary amine to the mixture obtained in c), and

[0338] e) obtaining a product comprising a hydroxybenzoic acid or hydroxyhydroquinone structure connected to a tertiary amine and further comprising a lipophilic tail group as defined above.

[0339] In a fifth aspect, there is provided an ionizable lipid nanoparticle comprising the compound according to the first aspect and the various embodiments related thereto or the lipid according to the second aspect and the embodiments related thereto.

[0340] In one embodiment, there is provided an ionizable lipid nanoparticle according to the various aspects, further comprising

[0341] structure lipids, wherein the structure lipid is phospholipid and / or sphingolipid, preferably wherein the phospholipid is selected from the group consisting of PC, PE, PA, PG, PI, PS and LPL, preferably wherein the sphingolipid is sphingomyelin, more preferably wherein the phospholipid is selected from the group of DSPC, DOPE, HSPC, DPPC, DSPG, DSPS and DPPA,

[0342] sterols, preferably wherein the sterol is cholesterol and / or sitosterol,

[0343] lipids modified with hydrophilic polymers, preferably wherein the lipid modified with hydrophilic polymers is PEGylated lipid, more preferably wherein the PEGylated lipid is DMG-PEG and / or DSPE-PEG and / or DSG-PEG,

[0344] and optionallySORT lipids, preferably wherein the SORT lipid comprises DODAP, DOTAP, DPDAB, DODMA, 14PA, 18BMP, 18PA, DC-cholesterol and / or 5A2-SC8,

[0345] and optionally

[0346] antioxidants and / or oils and / or fatty acids and / or fatty acid salts and / or surfactants.

[0347] In one embodiment the phospholipid may be connected to palmitoyloleoyl. In a certain embodiment PC may be of plant origin, such as GMO and NON-GMO. In another embodiment PC may be of animal origin. In yet another embodiment PC may be of synthetic origin. In one embodiment PC may be lecithin. In a certain embodiment lecithin is selected from the group consisting of soybean lecithin, sunflower lecithin and rapeseed lecithin.

[0348] In one embodiment PC is selected from the group consisting of DSPC, DPPC, HSPC, HEPC, DLPC, DEPC, DMPC, DOPC, DUPC, POPC, SOPC, ePC, sPC and hPC. In a preferred embodiment PC is DSPC and / or HSPC and / or DPPC. In one embodiment PE is selected from the group consisting of DOPE, POPE, DPPE, DMPE, SOPE and LPE. In a preferred embodiment PE is DOPE. In one embodiment PA is DPPA. In one embodiment PG is DSPG and / or DOPG and / or DPPG. In a preferred embodiment PG is DSPG. In one embodiment PS is DSPS.

[0349] In one embodiment the origin of the sterol is selected from the group consisting of plant, animal, fungi and synthetic. In a certain embodiment the sterol of animal origin is selected from the group consisting of cholesterol, lanosterol, komprosterol, cholestanol, lithocholic acid and cholic acid. In another embodiment the sterol of plant origin is selected from the group consisting of cholesterol, sitosterol, stigmasterol, campesterol and brassikasterol. In a further embodiment the sterol of fungi origin is ergosterol.

[0350] In one embodiment the lipid modified with hydrophilic polymers is selected from the group consisting of PEGylated diglyceride, PEGylated phospholipid, PEGylated sterol, PEG with a linker, lipid with lactic acid modification, lipid with polylactic acid modification, lipid with polylactic-co-glycolic acid modification, polysaccharide modified lipid and pSar lipid. In one embodiment the lipid modified with hydrophilic polymers comprises PEG 600. In another embodiment the lipid modified with hydrophilic polymers comprises PEG 2000. In yet another embodiment the lipid modified with hydrophilic polymers comprises PEG 5000. In one embodiment the PEGylated lipid is selected from the group consisting of DMG-PEG,DSPE-PEG, DSG-PEG, PEG-CER, PEG-DEG, PEG-DMPE, PEG-DPPC, PEG-c-DOMG, DPPE-PEG and c-DMA-PEG. In a preferred embodiment the PEGylated lipid is DMG-PEG and / or DSPE-PEG and / or DSG-PEG. In one embodiment the lipid modified with hydrophilic polymers comprises DMG-pSar25. In one embodiment the lipid modified with hydrophilic polymers comprises DOPE-pSar.

[0351] In one embodiment the antioxidant is selected from the group consisting of Vitamin E and its derivatives such as alpha-tocopherol, beta-tocopherol, gamma-tocopherol, tocotrienol and mixes thereof, carotenoids such as beta-carotene, lycopene, lutein and astaxanthin, resveratrol, lipoic acid and ubiquinone.

[0352] In one embodiment the oil is selected from the group consisting of medium-chain triglyceride, fish oil, olive oil and soybean oil.

[0353] In one embodiment the fatty acid is selected from a group selected from oleic acid, sodium acid, stearate and salts thereof.

[0354] In one embodiment the surfactant is selected from a group consisting of sorbitan esters such as, e.g., Span 20, Span 60 and Span 80, polysorbates such as, e.g., Polysorbate 20, Polysorbate 80 and Tween®, alkoxylated fatty acids, vegetable oil ethoxylates and ethoxylated fatty alcohols, such as, e.g., Brij® 35.

[0355] In one embodiment the ionizable lipid nanoparticle according to the various aspects further comprises at least one phenolic lipid. In one embodiment the ionizable lipid nanoparticle according to the various aspects further comprises at least one pSar lipid. In one embodiment the ionizable lipid nanoparticle according to the various aspects further comprises at least one polylactame. In one embodiment the ionizable lipid nanoparticle according to the various aspects further comprises at least one fatty alcohol. In one embodiment the ionizable lipid nanoparticle according to the various aspects further comprises at least one stearylated octaarginine. In one embodiment the ionizable lipid nanoparticle according to the various aspects further comprises at least one preservative. In one embodiment the ionizable lipid nanoparticle according to the various aspects further comprises at least one biocide.

[0356] In one embodiment the phenolic lipid is selected from a group consisting of anacardic acid, cardol and cardanol. In one embodiment the preservative is selected from a groupconsisting of benzyl alcohol, potassium sorbate, sodium benzoate, benzoic acid, phenoxyethanol.

[0357] In one embodiment, there is provided a method of producing an ionizable lipid nanoparticle according to fifth aspect via post-encapsulation of nucleic acid, preferably via RNA postencapsulation, particularly preferably via mRNA post-encapsulation. Preferably, the postencapsulation method to produce the LNP according to the invention refers to the method described by Tanaka et al. in “A Post-Encapsulation Method for the Preparation of mRNA-LNPs via the Nucleic Acid-Bridged Fusion of mRNA-Free LNPs”, 2025.

[0358] In a sixth aspect, there is provided a method of producing the ionizable lipid nanoparticles according to the fifth aspect and the embodiments related thereto,

[0359] wherein the method comprises the following steps, in sequence:

[0360] a) providing a lipid phase comprising a compound according to the invention, an ionizable lipid according to the invention or a product obtained according to the invention,

[0361] b) providing an aqueous phase, and

[0362] c) mixing the lipid phase provided in a) with the aqueous phase provided in b)

[0363] preferably wherein a microfluidic technique is used, and

[0364] d) obtaining a lipid nanoparticle.

[0365] In one embodiment the mixing can be carried out by a microfluidic technique. The microfluidic technique is based on both, turbulent and laminar flow. The lipid phase and the aqueous phase are introduced into microfluidic channels where they meet and mix. A microfluidic channel may have several geometries to provide a specific mixing efficiency, size control and scalability. In one embodiment the microfluidic channel can be selected from the group consisting of linear channel, multi-channel, "Y"-junction and "T"-junction and chaotic mixer. In one embodiment the mixing can occur under laminar flow to promote gentle and uniform mixing. In another embodiment the mixing can occur under turbulent flow which induces rapid mixing.In another embodiment the mixing can be carried out by an ethanol injection method. This method provides a rapid injection of a lipid-containing ethanol solution into an aqueous phase to facilitate the self-assembly of nanoparticles.

[0366] In yet another embodiment the mixing can be carried out by combining the lipid phase with the aqueous phase under controlled conditions to achieve a nanoparticle formation.

[0367] Downstream processes may include desalting, buffer exchange, concentration methods, centrifugal ultrafiltration and diafiltration, wherein spin columns and filters may be used. Further, there may be carried out tangential flow filtration, size exclusion chromatography, ion exchange chromatography and / or sterile filtration, and optionally freezing and / or lyophilisation.

[0368] In a seventh aspect, there is provided a composition comprising the compound or the ionizable lipid or the ionizable lipid nanoparticle according to the various aspects.

[0369] In a preferred embodiment the composition is a pharmaceutical composition. In another embodiment, the composition is a cosmetic composition. In yet another embodiment the composition is a nutritional composition. In a further embodiment the composition is an agricultural composition.

[0370] A “pharmaceutical composition” as used herein refers to a composition, preparation or product comprising at least one main ingredient or substance and, optionally, at least one carrier. It may be used as medicine, medical device, adjuvant and health care product. It can further be used to prevent or treat disorders and diseases, to improve health condition, to influence physiological functions or to enable medical diagnosis.

[0371] A “cosmetic composition” as used herein refers to a composition, preparation or product comprising at least one ingredient, wherein the ingredient or the whole formulation is / are used to change the external appearance or smell of the human or animal body in line with socially determined and / or individual ideals. It can further be used for body care and penetrating and permeating skin barriers.

[0372] A “nutritional composition” as used herein refers to a composition, preparation or product in the field of nutrition. Non limiting examples of nutritional compositions are a nutrition supplement product, a nutritional substitute product and a main nutritional product. The nutrition may be food in solid, semi-solid, liquid or gaseous food. The application form ofthe nutrition may be oral, parenteral, sublingual, buccal, subcutaneous, intramuscular, intravenous or inhalative. A nutritional composition according to the invention may be selected from the group consisting of a beverage, drink, meat-based food, vegetarian food, vegan food, artificial food, genetically modified food, bar, mush, emulsion, suspension solution, injection, infusion, aerosol, capsule, paste, gel, lozenge, granule, tablet, foam and spray.

[0373] An “agricultural composition” as used herein refers to a composition, preparation or product that can be used for application on and / or in the agricultural land, plants, grassland, arable land and livestock as well against a pathogen feeding on a plant, e.g. a pest and a parasite. Non limiting examples of agricultural compositions are a crop and and / or vegetable and / or fruit and / or ornamental protection product, a crop and and / or vegetable and / or fruit and / or ornamental growth product, a plant protection product, a plant growth product, a soil protection product, an animal feed, seeds, genetically modified plants, a herbicide and an insecticide.

[0374] In an eighth aspect, there is provided a use of the compound or a use of the ionizable lipid or a use of the ionizable lipid nanoparticle or a use of the composition according to the various aspects for the manufacture or preparation of a medicament for treatment and / or prevention of a disease or health condition as an active ingredient or as a cargo of an active ingredient.

[0375] In a ninth aspect, there is provided a use of the compound or a use of the ionizable lipid or a use of the ionizable lipid nanoparticle ora use of the composition according to the various aspects for the manufacture or preparation of a medicament for treatment and / or prevention of a disease or health condition as an active ingredient or as a cargo of an active ingredient,

[0376] wherein at least one disease selected from the group of cancer, inflammatory diseases, autoimmune diseases, destroyed tissue, psychological disorders, gastrointestinal diseases and respiratory diseases is / are treated and / or prevented.

[0377] In one embodiment, the compound or ionizable lipid or ionizable lipid nanoparticle or composition according to the various aspects may be used for recombinant protein production. In another embodiment, the compound or ionizable lipid or ionizable lipid nanoparticle or composition according to the various aspects may be used for immune modulating.In a certain embodiment, the dosage form of a cosmetic composition or a pharmaceutical composition is selected from the group consisting of solid dosage forms such as tablets, sublingual tablets, melting tablets, dragees, capsules, soft capsules, hard capsules, gastroresistant capsules, granules, powders and printlets, semi-solid dosage forms such as ointments, creams, pastes and gels, liquid dosage forms such as suspensions, crystal suspensions, emulsions, solutions, drops, nasal drops, eye drops, ear drops, syrups, juices, injection solutions, injection dispersions, injection solutions and injection solution concentrates, and further dosage forms such as suppositories, lozenges, effervescent tablets, effervescent powders, inhalation powders, plasters, metered dose inhalers, foams, sprays, sublingual sprays, shampoos, mouthwashes, vaginal suppositories, vaginal tablets and vaginal capsules.

[0378] In a certain embodiment, the application form of a cosmetic composition or a pharmaceutical composition is selected from the group consisting of aural, buccal, enteral, inhalative, intra-arterial (i.a.), intra-articular, intrabronchial, intraductal, intragluteal, intracardiac, intracavernous, intralesional, intralumbar, intralymphatic, intramammary, intramuscular (i.m.), intranasal, intraneural, intraocularintraosseous (i.o.), intraperitoneal (i.p.), intrapleural, intrapulmonary, intrathecal, intratracheal, intraurethral, intrauterine, intravenous, intraventricular, intravitreal, conjunctival, oral, parenteral, peroral, perineural, rectal, retrobulbar, subcutaneous (s.c.), sublingual, transdermal and vaginal.

[0379] Surprisingly it was found that the compounds being suitable for ionizable lipids along with the resulting ionizable LNPs according to the invention show high efficiency of molecule delivery to specific locations in target organisms. Fig. 1 & 2 show the efficient drug delivery in mice, wherein iLNPs according to the invention were used. Given that the invented products are able to pass through biomembranes, skin barrierers and even the blood-brain barrier, they can be used to deliver drugs precisely to a human target region or in cosmetic products. They are therefore just as suitable for delivering molecules to versatile target organisms like plant cells or organisms in the nutritional or agricultural sector.

[0380] In a tenth aspect, there is provided a use of the compound or the ionizable lipid or the ionizable lipid nanoparticle or the composition according to the various aspects as a cargo in a cosmetic product, in a nutritional product, in a diagnostic product, for recombinant protein production, or in an agricultural product.

[0381] In one embodiment, the compound or the ionizable lipid or the ionizable lipid nanoparticle or the composition according to the various aspects is used as a cargo in a cosmeticproduct to deliver mRNA encoding active biomolecules to skin cells to modulate gene expression.

[0382] In one embodiment, the delivered mRNA encodes antiaging peptides or proteins as active biomolecules, e.g. such as acetyl glycyl beta-alanine or dipeptide diaminobutyroyl benzylamide diacetate (e.g. SYN-AKE®). In another embodiment, the delivered mRNA encodes signal peptides or proteins as active biomolecules, e.g. such as matrikines (e.g. Matrixyl®). In yet another embodiment, the delivered mRNA encodes biomimetic peptides or proteins as active biomolecules. In a further embodiment, the delivered mRNA encodes grow factors as active biomolecules, e.g. such as epidermal growth factor (EGF). In still another embodiment, the delivered mRNA encodes neurotransmitter(s) as active biomolecules, e.g. such as argireline (acetyl hexapeptide-8).

[0383] In one embodiment, the delivered mRNA encodes biomolecules to skin cells to modulate gene expression involved in skin aging. In another embodiment, the delivered mRNA encodes biomolecules to skin cells to modulate gene expression involved in pigmentation. In yet another embodiment, the delivered mRNA encodes biomolecules to skin cells to modulate gene expression involved in inflammation. In a further embodiment, the delivered mRNA encodes biomolecules to skin cells to modulate gene expression involved in barrier repair.

[0384] In one embodiment, the compound or the ionizable lipid or the ionizable lipid nanoparticle or the composition according to the various aspects is used as a cargo in a nutritional product is administered orally. In another embodiment, the compound or the ionizable lipid or the ionizable lipid nanoparticle or the composition according to the various aspects is used as a cargo in a nutritional product is administered by injection.

[0385] In one embodiment, the compound or the ionizable lipid or the ionizable lipid nanoparticle or the composition according to the various aspects is used as a cargo in a nutritional product to deliver nutraceutical RNA encoding bioactive compounds to regulate metabolic pathways or support immune function.

[0386] In one embodiment, the delivered nutraceutical RNA encodes colostrum immunoglobulins. In another embodiment, the delivered nutraceutical RNA encodes lactoferrin. In yet another embodiment, the delivered nutraceutical RNA encodes collagen.In one embodiment, the compound or the ionizable lipid or the ionizable lipid nanoparticle or the composition according to the various aspects is used as a cargo in a diagnostic product to deliver RNA probes into cells to enable sensitive detection of mutations, disease biomarkers or mapping transcriptional activity.

[0387] In one embodiment, the compound or the ionizable lipid or the ionizable lipid nanoparticle or the composition according to the various aspects is used as a cargo for recombinant protein production to deliver mRNA encoding recombinant proteins into production cell lines enabling transient and scalable protein expression without genomic integration.

[0388] In one embodiment, the production cell lines are bacterial production cell lines. In another embodiment, the production cell lines are yeast production cell lines. In yet another embodiment, the production cell lines are insect production cell lines. In a further embodiment, the production cell lines are mammalian production cell lines.

[0389] In one embodiment, the compound or the ionizable lipid or the ionizable lipid nanoparticle or the composition according to the various aspects is used as a cargo in an agricultural product to deliver nucleic acid(s) to (a) plant(s).

[0390] In one embodiment, the delivered nucleic acid induces gene silencing or gene expression for crop protection. In another embodiment, the delivered nucleic acid induces gene silencing or gene expression for stress resistance. In yet another embodiment, the delivered nucleic acid induces gene silencing or gene expression for yield enhancement. Further aspects and advantages of the invention result from the following description of preferred embodiments and from the drawings along with the description of drawings according to the invention.

[0391] Examples

[0392] Cytotoxicity assay

[0393] Cytotoxicity analysis of SYV ionizable lipids was performed by the XTT cell viability assay.

[0394] The cytotoxic effects of lipids were evaluated in vitro by XTT cytotoxic assay. Hep-G2 cells were seeded in a 96-well plate at 30 000 cells / 100 pL and incubated for 24 hours. The medium was removed, cells were washed with PBS twice and the medium containing SYV ionizable lipids in concentrations: 10, 20, 40, 60, 100, 200, 400, 600, 800 and 1000 pM wasadded. Reference cells were prepared (non-treated) in wells adding fresh medium with 1% DMSO and blank (wells without cells). After 24 and 48-hours incubation, the XTT was added to each well. The cells were incubated for 3 hours. The absorbance was measured at wavelength 450 nm and reference wavelength 660 nm in the microplate reader. Cell viability data were expressed as experiments' means ± standard deviation (SD). All experiments were performed in triplicates. The specific absorbance was calculated as follows:

[0395] Abs = Abs450nm(test) - Abs450nm(blank) - Abs660nm(test)

[0396] and the relative cell viability (%) was compared to control cells and calculated using the following equation:

[0397]

[0398] The IC50 (half maximal inhibitory concentration) was calculated using ED50 Excel tool.

[0399] See Fig. 4, Fig. 12, Fig. 13 and Fig. 14.

[0400] See additional results in Fig. 15.

[0401] Surprisingly it was found that even a dose of 1000 pM of the presented ionizable lipids did not lead to cell death of 50 % of Hep-G2 cells.

[0402] In-vivo biodistribution of mRNA-LNPs

[0403] LNPs were prepared by nanoprecipitation method using Spark or Ignite (Precision Nanosystems Inc.). The obtained LNP suspensions were diluted 10-fold in PBS 150 mM or Tris 60 mM. LNP purification, buffer exchange, and formulation concentration were performed using MWCO 30000 filters (Merck). Particle size and polydispersity of the LNPs were measured using Zetasizer (Malvern) before and after purification. The mRNA encapsulation efficiency was determined by the Quant-iT Ribogreen RNA assay.

[0404] An experiment was conducted involving acclimatized mice (6-8 week-old female BALB / c mice) that were administered dispersion of provided test formulations. During the acclimatization period and throughout the experiment, the mice were housed in IVC cages(3 mice per cage) under standard environmental conditions: temperature 22 °C ± 2 °C, relative humidity 55% ± 10%, and a 12-hour light / dark cycle. The animals had free access to autoclaved rodent feed (Altromin 1324) and were provided with autoclaved water ad libitum.

[0405] To investigate the accumulation and decay of bioluminescence associated with the administered mRNA-LNP formulations (v=100pL), the test formulations were injected intravenously / into the tail vein of mice randomly divided into groups of 3 mice (in triplicate).

[0406] For imaging purposes, the mice were administered luciferase substrate, specifically luciferin, in the form of a potassium salt solution dissolved in PBS (15 mg / mL), into the dorsal fold. Depending on their body weight, the mice received volumes of this solution corresponding to the recommended dose of 150 mg / kg body weight, i.e., 3 mg of luciferin per 20 g mouse. Each mouse was weighed, and the luciferin doses were individually adjusted.

[0407] Approximately 5 minutes after luciferin administration and just before the start of imaging, the mice were anesthetized using 4% isoflurane in an induction chamber. Subsequently, after placing the mice in the MS Spectrum CT chamber on the imaging platform and maintaining anesthesia with 2% isoflurane delivered via a nose cone, bioluminescence imaging was performed over a 15-20 minute time period. During signal acquisition, bioluminescence signal parameters were recorded. For Group 1 , a 1-second acquisition was chosen at 4 hours and a 2-second acquisition at 24 hours; for the other groups, 2 and 5-second acquisitions were selected, respectively. At longer acquisition times (e.g., 1 minute, 15 seconds), the signal was oversaturated. Bioluminescence values were quantified by measuring photon flux (photons / second) in the region of interest (i.e., the entire mouse excluding the tail) from which the bioluminescence signal emanated, using Living IMAGE software (Caliper).

[0408] Bioluminescence imaging of the mice, reflecting the translational efficiency of the mRNA complexed with the carrier, was performed at two time points (24 and 48 hours post-intravenous injection of the provided formulations).

[0409] See Fig. 1, Fig. 2 and Fig. 3.

[0410] Jurkat Cells transfection mRNA encoding luciferaseThe aim was the evaluation of translational efficiency of lipofectamine Messenger Max and SyVento formulations on Jurkat cells model (T-cells) using Trilink Flue mRNA encoding luciferase.

[0411] Jurkat cells were seeded on a 96-well plate in the number 20 000 cells / well on the white opaque plate for luminescence readouts. The day before the seeding day, a Trilink mRNA mix with lipofectamine Messenger Reagent and Opti-MEM was prepared.

[0412] After 24 hours 5p I of mRNA-lipofectamine mix was gently pipetted and added for wells with cells to the following final concentrations: 500 ng / mL (50 ng mRNA per well), 200 ng / mL (20 ng mRNA per well), 100 ng / mL and (10 ng mRNA per well), then incubated for 24 hours in 37°C and 5% CO2.

[0413] Three formulations (SYV1_LG_1_230924, SYV2_LP_1_230924, SYV3_LO_1_230924) were diluted in PBS and added to cells in the following concentrations: 500 ng / mL (50 ng mRNA per well), 200 ng / mL (20 ng mRNA per well), 100 ng / mL and (10 ng mRNA per well), then incubated for 24 hours in 37°C and 5% CO2.

[0414] As a control formulation with reference lipid SM-102 was prepared and added to cells in final concentration: 1000 ng / mL (100 ng mRNA per well), 500 ng / mL (500 ng mRNA per well), 200 ng / mL (20 ng mRNA per well), 100 ng / mL (10 ng mRNA per well), 10 ng / mL (1 ng mRNA per well), then incubated for 24 hours in 37°C and 5% CO2.

[0415] The translational efficiency for plates was measured using the Bright-Glo™ Luciferase Assay (Promega) 24 hours after transfection - 105 pl of equilibrated to room temperature reagent was added to each well and then mixed gently. After 3 minutes luminescence was read using VarioScan Lux plate reader.

[0416] See Fig. 5, Fig. 6 and Fig. 7.

[0417] Assessment of target silencing efficiency

[0418] Table 1

[0419]

[0420]

[0421] Surprisingly it was found that Lipid F, Lipid O and Lipid P exceed D-Lin-MC3-DIVIA and C12-200 in the capacity of gene silencing.

[0422] Expression analysis of immune response-related factors

[0423] No significant changes in OAS1 expression were observed for the formulations comprising LNPs according to the invention.

[0424] See Fig. 11.

[0425] Target silencing effectiveness

[0426] Formulations comprising LNPs according to the invention loaded with siRNA lead to a surprisingly effective target silencing.

[0427] See Fig. 8, Fig. 9 and Fig. 10.

Claims

- 69 -Claims1. A compound being represented by formula (A) or formula (B) or formula (C) or a salt or stereoisomer thereof, preferably being suitable as lipid, particularly preferably being used as ionizable lipidformula (A),wherein n is 1 , 2, 3, 4, 5 or 6, preferably 1 , 2, 3 or 4, more preferably 2 or 3, and wherein Ri is an alkyl, a conjugated alkenyl, or an alkinyl, andwherein R2 is selected from the group consisting of H, COOH, benzyl, phenol, an alkyl, and a conjugated alkenyl, andwherein R3 and R4 are independently selected from the group consisting of H, NH2, benzyl, phenol, benzoic acid, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, an alkyl, and an alkenyl, andwherein R5 is selected from the group consisting of H, NH2, an alkyl, an alkenyl or an alkinyl, orformula (B),wherein Re is represented by formula (B-1)- 70 -formula (B-1),or a salt or stereoisomer thereof, andwherein m is 1 , 2, 3, 4, 5 or 6, preferably 2, 3, 4 or 5, particularly preferably 2 or 5, andwherein R? is represented by formula (B-1) or a salt or stereoisomer thereof, or is selected from the group consisting of H, an alkyl with a total number of carbon atoms in the range from 1 to 7, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group, andwherein Rs is represented by formula (B-1) or a salt or stereoisomer thereof, or is selected from the group consisting of H, an alkyl with a total number of carbon atoms in the range from 1 to 7, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group or a propanol group, andwherein Rg is selected from the group consisting of H, O-RBI or an alkyl, wherein RBI is H or an alkyl, and,when RBI is an alkyl, RBI has a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14 or 15, andwherein Rio is selected from the group consisting of H, O-RB2 or an alkyl, wherein RB2 is H or an alkyl, andwherein Rn is selected from the group consisting of H, O-RB3 or an alkyl, wherein RB3 is H or an alkyl, and- 71 -when RB3 is an alkyl, RB3 has a total number of carbon atoms of 1 , 2, 3 or 4 and / or wherein m is 5 and / or wherein Rio is O-RB2, andwhen Rio is O-RB2, RB2 is an alkyl with a total number of carbon atoms of 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, andwherein R12 is selected from the group consisting of H, O-RB4 or an alkyl, wherein RB4 is H or an alkyl, andpreferably wherein at least one of R9, R10, R11 or R12 is selected from the group consisting of O-RBI, O-RB2, O-RB3 or O-RB4, orformula (C),wherein k is 1 , 2, 3, 4, 5 or 6, preferably 2, 3, 4 or 5, particularly preferably 2 or 3, andwherein R13 is an alkyl, an alkenyl or an alkinyl, andwherein R14 is selected from the group consisting of H, a benzyl, an alkyl or an alkenyl, andwherein R15 is selected from the group consisting of H, a methanol group, an ethanol group, a propanol group, a butanol group, a pentanol group or an alkyl, and wherein R16 is selected from the group consisting of H, an ethanol group, a propanol group, a butanol group, a pentanol group or an alkyl.

2. The compound according to claim 1 , wherein the tertiary amine being represented as N in formula (A) or formula (B) or formula (C) is selected from the group of a tertiary aliphatic amine, a tertiary cyclic amine and a tertiary aromatic amine, preferably wherein the at least one tertiary amine is a tertiary cyclic amine or a tertiary aliphatic amine, particularly preferably a tertiary aliphatic amine.- 72 -3. The compound according to claim 1 or 2,wherein at least one of R-i, R2, R5, R9, R10, R11 and R12 is / are an alkyl, an alkenyl or an alkinyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, preferably with a total number of carbon atoms in the range from 6 to 24, more preferably wherein at least one of R1, R2, R5, R9, R10, R11 and R12 has a total number of carbon atoms of 10, 12, 13, 15, 16, 17 or 18,wherein the Ri-alkenyl and / or the R2-alkenyl is / are a conjugated alkenyl, preferably a conjugated alkenyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above,and / or wherein at least one of RBI, RB2, RB3 and RB4 is / are an alkyl.

4. The compound according to claim 3, wherein the alkyl representing RBI, RB2, RB3 and / or RB4 comprises one or more hetero atoms as chemical residue, preferably wherein the hetero atom(s) is / are oxygen atom(s),wherein R9 comprises a sole ether group being O-RBI as defined in formula (B-1 ), wherein R10 comprises a sole ether group being O-RB2 as defined in formula (B-1), wherein Rn comprises a sole ether group being O-RB3 as defined in formula (B-1), and / or wherein R12 comprises a sole ether group being O-RB4 as defined in formula (B-1).

5. The compound according to any of the preceding claims, wherein the compound is represented by formula (1), (2), (3), (4), (5), (6), (7), (8), (9), (11), (12), (13), (14), (18), (19), (20), (21), (22), (23), (24), (25), (26) or (27) or a salt or stereoisomer thereof, preferably being suitable as lipid, particularly preferably being used as ionizable lipidformula (1),- 73 -formula (2),formula (5),formula (6),- 74 -formula (9),formula (13),formula (19),- 77 -formula (22),formula (23),- 78 -formula (27).

6. An ionizable lipid comprising a hydroxybenzoic acid structure, wherein one tertiary amine is present and- 79 -wherein the tertiary amine has at least one chemical residue, wherein the chemical residue is selected from the group consisting of H, an alkyl, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group, a butyl group or a propanol group, orwherein the tertiary amine is a tertiary cyclic amine, preferably the being present as part of a pyrrolidine, a piperidine, a pyrrole or a pyridine structure, preferably a pyrrolidine or piperidine, andwherein not more than two ester groups are present, wherein the carboxyl group of the hydroxybenzoic acid has an alkyl, a conjugated alkenyl or an alkinyl as chemical residue, and wherein the tertiary amine is connected to the phenolic oxygen atom of the hydroxybenzoic acid via an alkyl group, orwherein the ionizable lipid has a chemical structure of formula (A) as defined in claim 1 , orwherein the ionizable lipid has a chemical structure of formula (B), wherein formula (B) includes formula (B-1), as defined in claim 1 ,preferably wherein one or two hydroxybenzoic acid(s) is / are present, preferably wherein the aromatic group of the hydroxybenzoic acid has H, an ether or an alkyl as a chemical residue,preferably wherein the tail group as chemical residue of the ether and / orthe aromatic group of the hydroxybenzoic acid and / or the oxygen atom of the carboxyl group is an alkyl, an alkenyl or an alkinyl with a total number of carbon atoms of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, more preferably with a total number of carbon atoms in the range from 6 to 24, particularly preferably with a total number of carbon atoms of 10, 12, 13, 15, 16, 17 or 18.

7. An ionizable lipid comprising a hydroxyhydroquinone structure,preferably wherein the ionizable lipid has a chemical structure of formula (C) as defined in claim 1 ,wherein one tertiary amine is present and- 80 -wherein the tertiary amine has at least one chemical residue, wherein the chemical residue is selected from the group consisting of H, an alkyl, a methanol group, an ethanol group, a propanol group, a butanol group or a pentanol group, preferably a methyl group, a butyl group or a propanol group, orwherein the tertiary amine is a tertiary cyclic amine, preferably the being present as part of a pyrrolidine, a piperidine, a pyrrole or a pyridine structure, preferably a pyrrolidine or piperidine, andwherein the tertiary amine is connected to the oxygen atom in position 4 of the hydroxyhydroquinone structure according to IUPAC nomenclature via an alkyl group, preferably wherein the two oxygen atoms in positions 1 and 2 of the hydroxyhydroquinone structure according to IUPAC nomenclature are connected via a carbon atom, more preferably wherein the connecting carbon atom has at least one alkyl with a total number of 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, or above, as chemical residue, particularly preferably with a total number of carbon atoms of 13.

8. A method of producing the compound according to any of claims 1 to 5, or the lipid according to claim 6 or 7,wherein the method comprises the following steps, in sequence:a) providing a raw material comprising a structure of hydroxbenzoic acid or a derivative or a salt thereof or a structure of hydroxyhydroquinone or a derivative or a salt thereof,b) mixing the provided raw material with a substance for elongating the tail group of the provided raw material,c) adding a substance to the mixture obtained in b) for hydrating a derivative of a hydroxyl group of the mixture obtained in b),d) adding a substance comprising a tertiary amine to the mixture obtained in c), and- 81 -e) obtaining a product comprising a hydroxybenzoic acid or hydroxyhydroquinone structure connected to a tertiary amine and further comprising a lipophilic tail group as defined in claims 1 to 5 or as defined in claims 6 or 7.

9. An ionizable lipid nanoparticle comprising the compound according to any of claims 1 to 5 or the lipid according to claim 6 or 7.

10. The ionizable lipid nanoparticle according to claim 9, further comprising structure lipids, wherein the structure lipid is phospholipid and / or sphingolipid, preferably wherein the phospholipid is selected from the group consisting of PC, PE, PA, PG, PI, PS and LPL, preferably wherein the sphingolipid is sphingomyelin, more preferably wherein the phospholipid is selected from the group of DSPC, DOPE, HSPC, DPPC, DSPG, DSPS and DPPA,sterols, preferably wherein the sterol is cholesterol and / or sitosterol,lipids modified with hydrophilic polymers, preferably wherein the lipid modified with hydrophilic polymers is PEGylated lipid, more preferably wherein the PEGylated lipid is DMG-PEG and / or DSPE-PEG and / or DSG-PEG,and optionallySORT lipids, preferably wherein the SORT lipid comprises DODAP, DOTAP, DPDAB, DODMA 14PA, 18BMP, 18PA, DC-cholesterol and / or 5A2-SC8, and optionallyantioxidants and / or oils and / or fatty acids and / or fatty acid salts and / or surfactants.

11. A method of producing the ionizable lipid nanoparticles according to claim 9 or 10, wherein the method comprises the following steps, in sequence:a) providing a lipid phase comprising a compound according to any of claims 1 to 5, an ionizable lipid according to claim 6 or 7 or a product obtained according to claim 8,b) providing an aqueous phase,- 82 -c) mixing the lipid phase provided in a) with the aqueous phase provided in b), preferably wherein a microfluidic technique is used, andd) obtaining a lipid nanoparticle.

12. A composition comprising the compound according to any of claims 1 to 5, the ionizable lipid according to claim 6 or 7 or the ionizable lipid nanoparticle according to claim 9 or 10,preferably wherein the composition is a pharmaceutical composition, a cosmetic composition, a nutritional composition or an agricultural composition.

13. A compound according to any of claims 1 to 5, or an ionizable lipid according to claim 6 or 7, or an ionizable lipid nanoparticle according to claim 9 or 10, or a composition according to claim 12 for use in a method of treatment and / or prevention as an active ingredient or as a cargo of an active ingredient.

14. A compound according to any of claims 1 to 5, or an ionizable lipid according to claim 6 or 7, or an ionizable lipid nanoparticle according to claim 9 or 10, or a composition according to claim 12 for use in a method of treatment and / or prevention as an active ingredient or as a cargo of an active ingredient,wherein at least one disease selected from the group of cancer, inflammatory diseases, autoimmune diseases, destroyed tissue, psychological disorders, gastrointestinal diseases and respiratory diseases is / are treated and / or prevented.

15. A use of the compound according to any of claims 1 to 5, or a use of the lipid according to claim 6 or 7, or a use of the ionizable lipid nanoparticle according to claim 9 or 10, or a use of the composition according to claim 12 as a cargo in a cosmetic product, in a nutritional product, in a diagnostic product, for recombinant protein production, or in an agricultural product.

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