Nanosystems as selective vehicles

Abstract

In the present invention, the development of various oil-in-water (O/W) nanoemulsions containing an oil phase or oil core, preferably selected from vitamin E or oleic acid, stabilized by a sphingolipid of the sphingomyelin type, and optionally other lipids such as phospholipids, cholesterol, octadecylamine, DOTAP (N-[1-(2,3-Dioleoyloxy) propyl]-N, N, N-trimethylammonium methyl-sulfate), and PEGylated derivatives (derivatives with polyethylene glycol), for use as a nanotech vehicle, in particular for the management of cancer and metastatic disease, is herein described. Said nanoemulsions can be functionalized with ligands capable of interacting or binding to receptors expressed on the cell membrane of tumor cells, and in particular capable of interacting or binding to receptors expressed on the membrane of primary and/or disseminated or metastatic tumor cells. Also, antitumor drugs or therapeutic biomolecules can be encapsulated in said nanoemulsions and, finally, contrast agents can be incorporated for their use in the in vivo diagnosis in said nanoemulsions.

1 . Oil in water (o/w) nanoemulsion, comprising:
 a. An aqueous phase;   b. An oily nucleus comprising α-tocopherol (vitamin E); and   c. Sphingomyelin.   
     
     
         2 . The nanoemulsion, according to  claim 1 , wherein said nanoemulsion is functionalized with at least one of the following elements
 a. Therapeutic molecules; and   b. Contrast agents.   
     
     
         3 . The nanoemulsion, according to  claim 2 , wherein said therapeutic molecules are selected from the list consisting of: antitumor drugs such as carmofur, etoposide docetaxel, 5-Fluoracil, paclitaxel, gemcitabine, and edelfosine, or derivatives thereof; anti-inflammatory or anti-angiogenic drugs, such as curcumin, verteporfin, and resveratrol; nucleic acids such as pDNAs, shRNAs, miRNAs or mRNAs; biomolecules such as peptides, antibodies or fragments thereof, and aptamers; or combinations thereof. 
     
     
         4 . The nanoemulsion, according to  claim 2 , wherein the contrast elements are selected from the list consisting of fluorophores, SPIONs or derivatives thereof, radioisotopes, perfluorohexane and octafluoropropane, or combinations thereof. 
     
     
         5 . The nanoemulsion, according to  claim 1 , wherein said nanoemulsion is functionalized with ligands suitable for cellular vehiculization. 
     
     
         6 . The nanoemulsion, according to  claim 5 , wherein said ligands are ligands capable of binding to the TAS1R3 receptor. 
     
     
         7 . The nanoemulsion, according to  claim 6 , wherein said ligands are selected from the list consisting of the brazzein-derived peptide or lactisole sweetener. 
     
     
         8 . The nanoemulsion, according to  claim 5 , wherein said nanoemulsion is functionalized with ligands against the leptin receptor, guanylyl cyclase, uroguaniline, uroguaniline modified with lysines, the extracellular fraction of an integrin, or RPM. 
     
     
         9 . The nanoemulsion, according to  claim 1 , wherein said nanoemulsion further comprises other membrane lipids, a cationic lipid, a polyamine, polyethylene glycol (PEG), other surfactants or coating polymers, or combinations thereof, arranged in the interface of the nanoemulsion. 
     
     
         10 - 11 . (canceled) 
     
     
         12 . The nanoemulsion, according to  claim 2 , wherein said nanoemulsion is functionalized with ligands suitable for cellular vehiculization. 
     
     
         13 . The nanoemulsion, according to  claim 3 , wherein said nanoemulsion is functionalized with ligands suitable for cellular vehiculization. 
     
     
         14 . The nanoemulsion, according to  claim 4 , wherein said nanoemulsion is functionalized with ligands suitable for cellular vehiculization. 
     
     
         15 . An in vivo diagnosis method comprising administering to a subject a nanoemulsion of  claim 1 . 
     
     
         16 . A method of treating a subject for a disease, the method comprising administering to the subject a nanoemulsion of  claim 1 . 
     
     
         17 . The method of  claim 16 , wherein the disease is cancer. 
     
     
         18 . The method of  claim 17 , wherein the cancer is selected from the group consisting of: breast cancer, melanoma, uveal melanoma, pancreatic cancer, lung cancer, prostate cancer, stomach cancer, head and neck cancer, sarcoma, glioblastoma, neuroblastoma, cancer of the colon or rectum, cancer of the head or neck, kidney cancer, bladder cancer, and hepatocarcinoma.