Amphoteric liposomes comprising neutral lipids

An amphoteric lipid, which lipid has an isoelectric point between 4.5 and 8.5, according to the general formula (I):

• (I) Amphoteric substance —Y—spacer—amphiphilic substance characterized in that
• (a) the amphoteric substance has at least one portion of cationic charge with a pKa value between 4 and 8 and/or at least one portion of anionic charge with a pKa value between 3 and 7 and optionally additional charge carriers,
• aa) said portion of cationic charge being selected from the group comprising imidazole, morpholine, piperazine, purine, pyridine and/or pyrimidine or derivatives thereof,
• bb) said portion of anionic charge being a carboxyl group which comprises acetic acid, bromoacetic acid, chloroacetic acid, acetoacetic acid, propionic acid, acrylic acid, butyric acid, crotonic acid, or carboxylic acids bound in the aliphatic chain;
• which comprises dicarboxylic acids that are mono-esterified or amidated or bound in the aliphatic chain;
• which comprises oligocarboxylic acids that are mono-esterified or amidated or bound in the aliphatic chain,
• (b) the spacer is a lower alkyl residue with up to 8 C atoms, with linear, branched or cyclic structure, with 0, 1 or 2 ethylenically unsaturated bonds, and 0-4 hydroxyl groups,
• (c) Y comprises —(C═O)—O—;
• —(C═O)—NH—, —NH—(C═O)—O—;
• —O—;
• —NH—;
• —CH═N—;
• —O—(O═C)—;
• —S—;
• —(O═C)—;
• —NH—(O═C)—;
• —O—(O═C)—NH—;
• —N═CH— and/or —S—S—,
• (d) the amphiphilic substance is a structure according to the general formula (II) or (III) or (IV):
• (II)
• wherein
• R1 and R2 independently are C8-C30 alkyl or acyl chains with 0, 1 or 2 ethylenically unsaturated bonds, and
• X is selected from the group comprising —O—(C═O)—;
• —NH—(C═O)—;
• —S—(C═O)—;
• —O—;
• —NH—;
• —S—;
• —N═CH—;
• —(O═C)—O—;
• —S—(O═C)—;
• —NH—(O═C)—;
• —N═CH—;
• and/or —S—S—;
• or
• wherein
• R1 and R2 independently are C8-C30 acyl chains with 0, 1 or 2 ethylenically unsaturated bonds, and
• X is —O—;
• or
• wherein
• R1 and R2 independently are C8-C30 alkyl chains with 0, 1 or 2 ethylenically unsaturated bonds, and
• X is absent or selected from the group consisting of —(C═O)—O—;
• —(C═O)—NH—;
• —(C═O)—S—;
• —NH—;
• —CH═N—;
• and/or —S—(O═C)—;
• (e) the amphiphilic substance is a 1,4- or 1,5-dicarboxylic acid such as aspartic acid, glutamic acid, malic acid, tartaric acid, citric acid, aconitic acid, citraconic acid and/or maleic acid esterified with linear C8-C30 alcohols, and/or
• (f) the amphiphilic substance is a 1,4- or 1,5-diamine of 3-aminoalanine, diaminobutyric acid, ornithine, or lysine amidated with linear C8-C30 fatty acids;
• and liposomes thereof.