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Nanosystems as selective vehicles

a technology of nanosystems and selective vehicles, applied in the field of medical devices, can solve problems such as complicated monitoring and treatment of nanosystems

Inactive Publication Date: 2021-09-09
SERVIZO GALEGO DE SAUDE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about developing nanoemulsions that can be used as a treatment for cancer and other metastatic diseases. These nanoemulsions contain an oil phase and are stabilized by a special type of lipid called sphingomyelin. They can also carry other drugs or contrast agents for diagnosis. The invention identifies specific receptors on tumor cells that can be targeted with these nanoemulsions, such as leptin receptor, guanylyl cyclase receptor, and integrins. The discovery allows for the functionalization of these nanoemulsions with ligands that can interact with these receptors and molecules, making them more effective in tumor cells. Overall, this patent describes a way to develop nanostructures that can be used for the treatment and diagnosis of cancer.

Problems solved by technology

The metastatic tumor cells exhibit a phenotype that generally differs from the cells of the primary tumor, being generally more resistant, which, together with the distal location, makes their monitoring and treatment especially complicated.

Method used

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  • Nanosystems as selective vehicles
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Examples

Experimental program
Comparison scheme
Effect test

example 1

on of the Nanoemulsions of the Invention

[0104]The preparation of the nanoparticles was carried out by means of the ethanol injection technique, for which a stock was prepared with the oil: surfactant ratio (sphingolipids in combination or not with other surfactants), necessary in each case (Organic phase, FO), and injected 100 μL (using a syringe of 0.5 mL insulin Myjector, U-100 Insulin, Terumo) on 900 μL of H2O (aqueous phase, FA) contained in a small vial of 2 mL, and under magnetic stirring. The formation of oil-in-water (O / W) nanoemulsions occurred spontaneously under these conditions, presenting a spherical morphology and giving places to homogenous populations (FIG. 1). The structure consists of an oil core stabilized by sphingomyelin and sometimes other lipids, and are in principle suitable systems for the encapsulation in the nucleus of hydrophobic molecules, being able to associate also another type of amphiphilic or hydrophilic molecules, which will be arranged preferably...

example 2

ion of HPLC Methods

[0106]High performance liquid chromatography (HPLC) was used to determine the association to the developed nanostructures, both of the associated ligands, and of the therapeutic molecules of interest.

[0107]For the optimization of the methods, the characteristics of each molecule were taken into account. As for the ligands, the compounds described in Table 2 are contemplated, which after their incorporation into the formulation, give rise to functionalized nanoemulsions as those shown in Table 3. In the case of the peptides, the analysis was carried out at 220 nm, with a combination of water and acetonitrile as the mobile phase, usually less than 60% acetonitrile being sufficient for elution. It was also important to add in the mobile phase a small percentage of TFA (0.2%), an ion-pairing agent, highly used at its high volatility (Agilent, 2013), which allows the separation of ionic substances on phase HPLC columns. reverse by controlling retention and selectivity....

example 3

lization of the Nanosystems

[0110]The developed nanosystems were functionalized with the ligands mentioned in table 3. The characterization of said developed nanosystems was performed in terms of size, dispersion, and surface charge, in the same way as in the case of nanoemulsions without functionalization (example 1). Next, the procedure followed is grouped by the type of preparation in four cases.

3.1. Functionalization with Lipid Conjugates of Peptides, LAPI, UROG y RPM (V:SM:LAPI 1:0,1:0,01, O:SM:UROG 1:0,2:0,01, y V:SM:RPM 1:0,1:0,05)

[0111]The association of this ligand to nanoemulsions was made by adding 50 μL of a stock of each of the derivatives after dissolution in ethanol (at a concentration of 1 mg / ml in the case of LAPI and UROG, or 0.5 mg / ml for RPM, to the organic phase, which was then injected with 1 ml of water under stirring, to obtain the functionalized nanoemulsions.

3.2. Functionalization with the Hydrophilic Peptides (Cationic Peptide Derived from Uroguaniline O:SM...

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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.

Description

STATEMENT REGARDING SEQUENCE LISTING[0001]The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is 370093_402USPC_SEQUENCE_LISTING.txt. The text file is 2.83 KB, was created on Feb. 9, 2021, and is being submitted electronically via EFS-Web.FIELD OF THE TECHNIQUE[0002]The present invention belongs to the medical field, in particular to the field of pharmacological vehicles with nanotheranostic potential, in particular for the approach to cancer and the management of primary tumors and metastatic disease, the encapsulation of antitumor drugs and / or, finally, for the incorporation of a contrast agent for its use in in vivo diagnosis.BACKGROUND OF THE INVENTION[0003]The present invention offers a new pharmacological tool with nanotheranostic potential.[0004]A nanotechnology is a system that can combine elements of ...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K9/107A61K47/22A61K47/24A61K51/12A61K49/00A61K47/64A61K47/54A61K31/7048A61K31/513A61K31/337A61K31/7068A61K31/12A61K31/05A61K41/00A61K31/685A61K45/06A61P35/00A61K47/10
CPCA61K47/6907A61K47/10A61K47/22A61K47/24A61K51/122A61K49/0078A61K47/64A61K47/549A61K49/0002A61K31/7048A61K31/513A61K31/337A61K31/7068A61K31/12A61K31/05A61K41/0071A61K31/685A61K45/06A61P35/00A61K47/6425A61K9/1075A61K47/12A61K47/14A61K47/44A61K49/0017A61K49/101A61K49/1806A61K49/1818
Inventor DE LA FUENTE FREIRE, MARÍALÓPEZ LÓPEZ, RAFAELLÓPEZ BOUZO, BELÉNVÁZQUEZ RÍOS, ABI JUDITALONSO NOCELO, MARTA
Owner SERVIZO GALEGO DE SAUDE