Liposome compositions and medical uses thereof
OwnerPeter Buhl JENSEN, Ulla BUHL +5inventors
InventorsPeter Buhl JENSEN, Ulla BUHL, Thomas JENSEN, Steen KNUDSEN, Anker HANSEN, Mogens Winkel MADSEN, Ulrik LASSEN
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Abstract
The present disclosure describes liposomes comprising an anti-cancer agent, for example cisplatin and their use in treatment of cancer patients, for example subgroups of cancer patients.
Claims57
A liposome comprising:
- a) an anti-cancer agent, for example cisplatin, and
- b) one or more amphiphilic molecules.
The liposome according to any one of the preceding claims, wherein the anti-cancer agent is an ototoxic platinum-based anti-cancer agent.
The liposome according to any one of the preceding claims, wherein the anti-cancer agent is a platinum-based anti-cancer agent selected from the group consisting of:
- cisplatin and carboplatin.
The liposome according to any one of the preceding claims, wherein the one or more amphiphilic molecules are capable of or suitable for assembling into a liposome.
The liposome according to any one of the preceding claims, wherein the liposome is of pharmaceutical grade.
The liposome according to any one of the preceding claims, wherein the one or more amphiphilic molecules are selected from the group consisting of:
- phospholipids, glycolipids, steroids, fatty acids, fatty sulphates, amphiphilic peptides, polyesters, polyamides, polyurethanes, poly(lactic-co-glycolic acid) (PLGA) polymers, and co-block polymers comprising PEG.
The liposome according to any one of the preceding claims, wherein the liposome comprises a plurality of different amphiphilic molecules.
The liposome according to any one of the preceding claims, wherein the plurality of different amphiphilic molecules comprises an anionic lipid, a neutral lipid, and a polymer conjugated lipid.
The liposome according to any one of the preceding claims, wherein the liposome comprises between 20% and 45% of an anionic lipid.
The liposome according to any one of the preceding claims, wherein the liposome comprises between 40% and 75% of a neutral lipid.
The liposome according to any one of the preceding claims, wherein the liposome comprises between 3% and 6% of a polymer conjugated lipid.
The liposome according to any one of the preceding claims, wherein the anionic lipid comprises a phospholipid selected from the group consisting of PI (phosphatidyl inositol), PS (phosphatidyl serine), DPG (bisphosphatidyl glycerol), PA (phosphatidic acid), PEOH (phosphatidyl alcohol), and PG (phosphatidyl glycerol).
The liposome according to any one of the preceding claims, wherein the anionic lipid is a phospholipid selected from the group consisting of DSPI (distearoyl phosphatidyl inositol), DSPS (distearoyl phosphatidyl serine), DSDPG (distearoyl bisphosphatidyl glycerol), DSPA (distearoyl phosphatidic acid), DSPEOH (distearoyl phosphatidyl alcohol), and DSPG (distearoyl phosphatidyl glycerol), wherein the lipid comprises two stearoyl chains.
The liposome according to any one of the preceding claims, wherein the neutral lipid is distearoylphosphatidylcholine (DSPC).
The liposome according to any one of the preceding claims, wherein the polymer conjugated lipid is DSPE-PEG, such as DSPE-PEG-2000.
The liposome according to any one of the preceding claims, wherein the liposome comprises a polymer conjugated lipid, wherein the polymer is PEG and the PEG is selected from PEG-500 to PEG-5000, such as from PEG-1000 to PEG-4000, such as from PEG-1500 to PEG-3500, for example PEG-2000.
The liposome according to any one of the preceding claims, wherein the liposome comprises an amphiphilic molecule selected from the group consisting of:
- PEG [poly(ethylene glycol)], PAcM [poly(N-acryloylmorpholine)], PVP [poly(vinylpyrrolidone)], PLA [poly(lactide)], PG [poly(glycolide)], POZO [poly(2-methyl-2-oxazoline)], PVA [poly(vinyl alcohol)], HPMC (hydroxypropylmethylcellulose), PEO [poly(ethylene oxide)], chitosan [poly(D-glucosamine)], PAA [poly(aminoacid)], polyHEMA [Poly(2-hydroxyethylmethacrylate)] and co-polymers thereof.
The liposome according to any one of the preceding claims, wherein the liposome is hydrolysable under physiological conditions, for example in cancerous tissue.
The liposome according to any one of the preceding claims, wherein the liposome comprises:
- a) 1,2-distearoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (DSPG);
- b) 1,2-distearovl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000)] (DSPE-PEG);
- c) 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC);
- at a mol ratio of:
- 25:5:70 of a), b) to c),
- d) less than 1% cholesterol, and
- e) cisplatin.
The liposome according to any one of the preceding claims, wherein
- a) an interior of the liposome comprises 0.9% NaCl;
- b) a buffer solution on an exterior of the liposome comprises 10 mM phosphate buffer at pH 6.5, 1 mM NaCl and 10% sucrose;
- and/or
- c) the liposome is unilamellar.
A plurality of liposomes as defined in any one of the preceding claims, wherein the plurality of the liposomes is characterized by a diameter of from 50 to 400 nm, such as from 80 to 160 nm, for example 90 to 120 nm.
A plurality of liposomes as defined in any one of the preceding claims, wherein the plurality of the liposomes is characterized by a polydispersity index (PDI) of 0.2 or less, such as 0.10 or less.
A pharmaceutical composition comprising the liposome as defined according to any one of the preceding claims.
A liposome or a pharmaceutical composition as defined in any one of the preceding claims, for use in the treatment of a cancer in a patient.
The liposome or pharmaceutical composition for use according to any one of the preceding claims, wherein the liposome or pharmaceutical composition is administered to the patient in combination with one or more further anti-cancer agents.
Dependencies are inferred from the claim text.