Nanoparticles, composed of sterol and saponin from
A nanoparticle comprising at least one sterol, e.g. cholesterol and a component from Quillaja Saponaria Molina (QuilQ) selected from quillaja saponin, characterized in that said nanoparticles do not comprise a phospholipid and in that the sterol molecule is bound by a hydrophobic bond between a hydroxyl group of the sterol and terpene moieties in a Quil A micelle and by an hydrophilic ester bond between a sterol OH − and COOH − or aldehyde groups in the QuilA micelle. It also relates to a composition comprising the nanoparticles, and the use thereof as adjuvant, especially in vaccines, as carriers for amphipathic or hydrophobic molecules and as agents for treatment of cancer. Further, it regards a method for producing the phospholipid-free nanoparticles, a method for the treatment of cancer and a method for assessing the applicability of the cancer treating method.
1. A nanoparticle composed of two components and lacking phospholipid, the nanoparticle formed from a sterol membrane and a quillaja saponin micelle in an aqueous solution and having a particle diameter in the range of 12-35 nanometers.
2. The nanoparticle according to claim 1 , wherein sterol molecules of the sterol membrane are bound by a hydrophobic bond between a hydroxyl group of the sterol molecules and terpene moieties in the quillaja saponin micelle and by a hydrophilic hydrogen bond between a Off in the sterol molecules and a COOH − group or an aldehyde group in the quillaja saponin micelle.
3. The nanoparticle according to claim 1 , wherein the sterol is cholesterol.
4. The nanoparticle according to claim 1 , further having one or more of the following characteristics:
a particle diameter in the range of 15-25 nanometers,
the particle is built of 6 nm hexagonal rings built up by sterol and quillaja molecule subunits,
the molar ratio of sterol versus quillaja saponin in the particle is 1:2 to 2:1, or
several particles are densely packed, well dispersed and colloidal in water.
5. The nanoparticle according to claim 4 having a particle diameter in the range of 17-20 nanometers.
6. The nanoparticle according to claim 1 , wherein the nanoparticle comprises saponin selected from raw saponin, non-fractioned saponin, and fractions of saponin which contain fatty acids.
7. The nanoparticle according to claim 6 , wherein the fractions of saponin which contain fatty acids are selected from saponin fractions 15-22, saponin fraction B, saponin fraction C, and mixtures thereof.
8. The nanoparticle according to claim 1 , wherein the nanoparticle comprises a fraction of saponin that does not comprise fatty acids.
9. The nanoparticle according to claim 1 , wherein the nanoparticle comprises deacylsaponins.
10. The nanoparticle according to claim 1 , wherein the nanoparticle comprises saponin fractions 7-14, saponin fraction A, or a mixture thereof.
11. The nanoparticles according to claim 1 , wherein the weight ratio between sterol and quillaja saponin is from 1:2 to 2:1.
12. The nanoparticle according to claim 1 , further comprising at least one amphipathic molecule or a hydrophobic molecule.
13. The nanoparticle according to claim 12 , wherein the amphipathic molecule or hydrophobic molecule is selected from an antigen, an adjuvant, a targeting molecule, and a pharmaceutical compound.
14. The nanoparticle according to claim 12 , wherein the amphipathic molecule or the hydrophobic molecule is selected from the group consisting of diterpen (DT), VLX40, Busulfan, roscovitine, and vitamin D 3 .
15. A composition comprising a first nanoparticles according to claim 1 , the first nanoparticle comprising a first quillaja saponin fraction, and a second nanoparticle according to claim 1 , the second nanoparticle comprising a second quillaja saponin fraction, wherein the first quillaja saponin fraction and the second quillaja saponin fraction are different.
16. The composition according to claim 15 , wherein the first quillaja saponin fraction and the second quillaja saponin fraction are each independently selected from the group consisting of: crude Quil A, fraction A of Quil A, fraction C of Quil A, fraction B of Quil A, any fraction between fraction C and fraction B of Quil A, fraction C and one or more other fractions of Quil A; fraction C and fraction A of Quil A, fraction B and one or more other fractions of Quil A; and fraction B and fraction A of Quil A.
17. A pharmaceutical composition comprising: (i) the nanoparticle according to claim 1 ; and (ii) an acceptable buffer, diluent, excipient, adjuvant, carrier, or combination thereof.
18. A pharmaceutical composition according to claim 17 , further comprising at least one pharmaceutically active compound selected from the group consisting of anticancer drugs, and receptors for antibodies or monoclonal antibodies selected from a Fc receptor or a DD of Protein A of Staphylococcus Aureus.
19. An adjuvant composition comprising: (i) the nanoparticle according to claim 1 ; and (ii) an acceptable buffer, diluent, excipient, carrier, or combination thereof.
20. The adjuvant composition according to claim 19 further comprising diterpen (DT).
21. A vaccine composition comprising the adjuvant composition of claim 19 .
22. A vaccine composition comprising the adjuvant composition of claim 20 .
23. A vaccine composition according to claim 21 further comprising a structural protein of an influenza virus strain.
24. A vaccine composition according to claim 22 further comprising a structural protein of an influenza virus strain.
25. A pharmaceutical composition according to claim 18 , wherein the anticancer drug is selected from the group consisting of platinum coordination compounds, taxane compounds, camptothecin compounds, anti-tumour vinca alkaloids, anti-tumour nucleoside derivatives, nitrogen mustard or nitrosourea alkylating agents, anti-tumour anthracycline derivatives, trastzumab and anti-tumour podophyllotoxin derivatives, antimetabolites, inhibitor of mammalian target of rapamycin (mTOR), Cytarabine, Daunorubicin, Paclitaxel, Docetaxel, Cabazitaxel, Torisel, and Trabectedin.