Nanoparticles, Composed of Sterol and Saponin From Quillaja Saponaria Molina Process for Preparation and Use Thereof as Carrier for Amphipatic of Hydrophobic Molecules in Fields of Medicine Including Cancer Treatment and Food Related Compounds

Abstract

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 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 .- 20 . (canceled) 
     
     
         21 . A method for treatment of cancer, comprising administering to a patient in need thereof a pharmaceutically effective amount of nanoparticles, the nanoparticles comprising a sterol membrane and a quillaia saponin micelle having a particle diameter in the range of 12-35 nanometers. 
     
     
         22 . The method for treatment of cancer according to  claim 21 , wherein said cancer is leukaemia. 
     
     
         23 .- 31 . (canceled) 
     
     
         32 . The method of  claim 21 , wherein the nanoparticles lack a phospholipid. 
     
     
         33 . The method of  claim 21 , wherein the nanoparticles are formed from the sterol membrane and the quillaja saponin micelle in an aqueous solution. 
     
     
         34 . The method of  claim 21 , 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 OH −  in the sterol molecules and a COOH −  group or an aldehyde group in the quillaja saponin micelle. 
     
     
         35 . The method of  claim 21 , wherein the sterol is cholesterol. 
     
     
         36 . The method of  claim 21 , wherein the nanoparticles have one or more of the following characteristics:
 (a) a particle diameter in the range of 15-25 nanometers   (b) the particle is built of 6 nm hexagonal rings built up by sterol and quillaja molecule subunits,   (c) the molar ratio of sterol versus quillaja saponin in the particle is 1:2 to 2:1, or   (d) several particles are densely packed, well dispersed and colloidal in water.   
     
     
         37 . The method of  claim 21 , wherein the nanoparticles comprise saponin selected from raw saponin, non-fractioned saponin, and fractions of saponin which contain fatty acids. 
     
     
         38 . The method of  claim 21 , wherein the nanoparticles comprise saponin fractions 7-22, saponin fraction A, saponin fraction B, saponin fraction C, and mixtures thereof. 
     
     
         39 . The method of  claim 38 , wherein the cancer comprises solid tumor cells and the saponin fraction comprises saponin fraction A. 
     
     
         40 . The method of  claim 38 , wherein the cancer comprises non-solid tumor cells and the saponin fraction comprises saponin fraction C. 
     
     
         41 . The method of  claim 21 , wherein the nanoparticles further comprise at least one amphipathic or hydrophobic molecule. 
     
     
         42 . The method of  claim 41 , wherein the at least one amphipathic or hydrophobic molecule is an anticancer drug. 
     
     
         43 . A method for treatment of cancer, comprising administering to a patient in need thereof a pharmaceutically effective amount of a composition comprising
 (a) a first plurality of nanoparticles comprising a sterol membrane and a first quillaja saponin micelle and   (b) a second plurality of nanoparticles comprising a sterol membrane and a second quillaja saponin micelle,   wherein the first quillaja saponin micelle comprises a first quillaja saponin fraction and the second quillaja saponin micelle comprises a second quillaja saponin fraction, the first quillaja saponin fraction different than the second quillaja saponin fraction.   
     
     
         44 . The method of  claim 43 , wherein the first saponin fraction and the second 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. 
     
     
         45 . The method of  claim 43 , wherein the first plurality of nanoparticles and the second plurality of nanoparticles lack a phospholipid. 
     
     
         46 . A method for the treatment of cancer comprising administering to a patient in need thereof a pharmaceutical composition comprising
 (a) a nanoparticle, the nanoparticle comprising a sterol membrane and a quillaja saponin micelle having a particle diameter in the range of 12-35 nanometers,   (b) at least one pharmaceutically active compound, and   (c) an acceptable buffer, diluent, excipient, adjuvant, carrier, or combination thereof.   
     
     
         47 . The method of  claim 46 , wherein the at least one pharmaceutically active is an anticancer drug or a steroid. 
     
     
         48 . The method of  claim 47 , 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, alkylating antineoplastic agents, cyclin-dependent kinase (CDK) inhibitors, antimetabolites, inhibitor of mammalian target of rapamycin (mTOR), Cytarabine, Daunorubicin, Paclitaxel, Docetaxel, Cabazitaxel, Torisel, Trabectedin, VLX40, busulfan, and roscovitine. 
     
     
         49 . The method of  claim 46 , wherein the nanoparticle lacks a phospholipid. 
     
     
         50 . The method of  claim 46 , wherein the nanoparticles comprise saponin fractions 7-22, saponin fraction A, saponin fraction B, saponin fraction C, and mixtures thereof. 
     
     
         51 . The method of  claim 50 , wherein the cancer comprises solid tumor cells and the saponin fraction comprises saponin fraction A. 
     
     
         52 . The method of  claim 50 , wherein the cancer comprises non-solid tumor cells and the saponin fraction comprises saponin fraction C.