NANOCONTAINERS FOR THE TRANSPORT OF NON-POLAR, LIPOPHILIC SUBSTANCES SUCH AS ANTIBIOTICS

Description

[0001] The present invention relates to nanocontainers suitable as a novel delivery form for nonpolar, lipophilic compounds such as antibiotics, particularly for the treatment of serious infectious diseases. Based on a simple, water-based synthesis, a broad range of nonpolar, lipophilic compounds with a wide range of active ingredients and therapeutic applications is available. Furthermore, a simple combination of drug release with optical detection is possible. The nanocontainers according to the invention thus combine therapy (drug release) and diagnostics (optical detection of reagents).

[0002] Nonpolar, lipophilic compounds, especially active pharmaceutical ingredients, are often excluded from effective clinical use because they cannot be administered, or can only be administered with great difficulty, and / or reach the site of action only in insufficient concentrations. This is particularly true when lipophilic compounds are administered intravenously via the bloodstream or when they are to be introduced into aqueous environments (e.g., alveoli). Furthermore, the cellular uptake or transport across membranes of nonpolar, lipophilic compounds is often significantly reduced compared to polar, hydrophilic compounds.

[0003] In principle, a whole range of highly effective antibiotics, some of which have been known for a long time, are available for a wide variety of applications and therapies. However, these antibacterial agents must not only penetrate granuloma encapsulations and the membrane of host cells, but also, if necessary, the lipid-rich cell walls of mycobacterial cells. Further limitations include their low permeability in biofilms and their rapid degradation under physiological conditions at low doses, but severe side effects at higher doses. Conversely, insufficient doses are the main reason for general treatment failure and the primary risk factor for bacterial multi-resistance.

[0004] Against this background, cost-effective and efficient active ingredients and delivery systems are needed to achieve lower dosages and shorter treatment durations while avoiding side effects. This would increase patient compliance and minimize the risk of therapeutic failures and bacterial resistance. Nanomaterials already offer promising strategies for molecular biology and medicine. Their use in novel imaging techniques and tumor therapy has been intensively investigated in recent years. For treatment with active ingredients such as antibiotics, equally efficient delivery systems for infiltrating the antibiotics into infected cells would be required. Such delivery systems should ideally contain the highest possible concentration of antibiotics and also be biocompatible, readily biodegradable, and, ideally, completely eliminated after two to three days. Such nanoscale delivery systems have so far received little attention.In particular, SiO₂ and polymer nanoparticles have been coated or loaded with antibiotics, although the antibiotic content relative to the total mass of the nanoparticles is low (i.e., antibiotic loading < 10 wt%). The inert carrier system thus constitutes the majority component (> 90 wt%). The carrier system generally has no efficacy. However, it can present a number of disadvantages, ranging from side effects and toxic effects to insufficient biodegradability. Furthermore, most nanoparticulate systems are used for the transport of polar, hydrophilic antibiotics.

[0005] As a concrete example, tuberculosis (TB) can be cited, which, according to the World Health Organization (WHO), is one of the world's most widespread infectious diseases with a high mortality rate. In 2013, for instance, approximately 9 million cases of TB were reported, resulting in 1.5 million deaths. TB has recently regained considerable importance in connection with HIV and as a result of the alarming multidrug-resistant (MDR) and extremely drug-resistant (XDR) isolates. Furthermore, it is estimated that about one-third of the world's population is latently infected, with the probability of an acute course of the disease being around 10% over a lifetime. The pathogenic agent, M . tuberculosis ( M.tb. ) ,It is found as a facultative intercellular parasite encapsulated in granulomas within macrophages. Against this background, latent tuberculosis in particular presents a major challenge. Suitable nonpolar, lipophilic agents include, for example, delamanid, bedaquiline, benzothiazone (BTZ), amikazine, clofazimine, levofloxacin, and pantoprazole.

[0006] Other use cases relate to multi-resistant bacteria such as Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii or various Enterobacter types, which have become known as "hospital germs" and lead to high death rates in hospitals.

[0007] These two applications are representative of many other bacterial diseases and can each be described as mass-market applications, which clearly demonstrates their relevance. Alongside new antibiotics, new, efficient dosage forms are of equal urgency and relevance. Patent WO 2012 / 071014 discloses core-shell particles, each comprising: a core containing a hydrophobic polymer with an anionic group; and a shell containing calcium phosphate, wherein at least one of the calcium atoms contained in the calcium phosphate is chemically bonded to a functional group derived from the anionic group.

[0008] Against this background, the object of the present invention is to provide a biocompatible and readily degradable delivery form for nonpolar, lipophilic compounds with a very broad range of applications, which allows a large loading amount of nonpolar, lipophilic compound and at the same time permits optical detection and which is accessible via a very simple synthesis, as well as a cost-effective and efficient method for producing this delivery form.

[0009] This problem is solved by the embodiments characterized in the claims.

[0010] In particular, according to the invention, a nanocontainer according to claim 1 is provided, comprising an emulsion comprising at least one nonpolar, lipophilic compound encapsulated by a biocompatible surfactant having at least one polar group selected from a phosphate group, a sulfate group, a sulfonate group or a carboxyl group, and an inorganic, biocompatible shell that encloses the emulsion, wherein the polar group is ionically bound to the inorganic, biocompatible shell and thereby the surfactant, due to its orientation, lipophilizes the cavity of the inorganic shell.

[0011] The nanocontainer according to the invention comprises an emulsion containing at least one nonpolar, lipophilic compound. This at least one nonpolar, lipophilic compound is encapsulated by a biocompatible surfactant having at least one polar group selected from a phosphate group, a sulfate group, a sulfonate group, or a carboxyl group. The surfactant also has a nonpolar, hydrophobic residue. The nanocontainer according to the invention further comprises an inorganic, biocompatible shell that encloses the emulsion. The polar group of the biocompatible surfactant is ionically bound to the inorganic, biocompatible shell, whereby the nonpolar residue of the surfactant points into the cavity of the shell, i.e., into the (hollow) space enclosed by the shell. The surfactant is thus located within the biocompatible shell, i.e., within the (hollow) sphere. This orientation of the surfactant lipophilizes the cavity of the inorganic shell.The inorganic, biocompatible shell mechanically stabilizes the emulsion through the structure of the nanocontainer according to the invention, thus making it available as a transport and storage form. According to the invention, the surfactant and the nonpolar, lipophilic compound are therefore encapsulated within the (hollow) sphere, i.e., within the shell.

[0012] According to the invention, the term "nonpolar, lipophilic compound" refers to compounds that are essentially insoluble in water (e.g., < 0.01 g / L) and very soluble (e.g., > 0.1 g / L) in alkanes, such as hexane and dodecane, and / or aromatic hydrocarbons, such as toluene and tocopherol. The emulsion of the nanocontainer according to the invention can comprise one or more nonpolar, lipophilic compounds. According to the invention, nonpolar, lipophilic compounds are pharmaceutical active ingredients and / or detection reagents. If a pharmaceutical active ingredient and a detection reagent are used in combination, the nanocontainer according to the invention can advantageously release the active ingredient after administration and be localized in, for example, cells, tissues, and organs due to the detection reagent.

[0013] According to the invention, the term "pharmaceutically active substance" means a substance that is used as a means for the cure or prevention of human or animal diseases, as well as a substance that is intended to be used in or on the human or animal body to restore, improve or influence the human or animal body functions.

[0014] According to one embodiment of the present invention, the pharmaceutically active ingredient is selected from der Gruppe der Antibiotika, bestehend aus Delamanid, Bedaquilin, Benzothiazon, Amikazin, Clofazimin, Levofloxacin, Ofloxacin, Rifampicin, Pantoprazol, Pyrimethamin, Trimethoprim, Sulfamethoxazol, Sulfadoxin, Novobiocin, Coumermycin, Clorobiocin, Metronidazol, Norfloxacin, Enoxacin, Ciprofloxacin, Ofloxacin, Levofloxacin, Moxifloxacin, Tigecyclin, Tetracyclin, Gentamicin, Kanamycin, Neomycin, Netilmicin, Streptomycin, Tobramycin, Chloramphenicol, Fusidinsäure, Cethromycin, Narbomycin, Telithromycin, Lincomycin, Daptomycin, Dalfopristin, Quinupristin, Azithromycin, Clarithromycin, Erythromycin, Roxithromycin, Linezolid, Doxycyclin, Minocyclin, Tetracyclin, Oxytetracyclin, Tigecyclin Imipenem, Meropenem, Ertapenem, Aztreonam, Benzylpenicillin, Phenoxymethylpenicillin, Piperacillin, Mezlocillin, Ampicillin, Amoxicillin, Flucloxacillin, Methicillin, Oxacillin, Clavulansäure, Sulbactam, Tazobactam, Sultamicillin, Teicoplanin, Vancomycin, Bacitracin, Colistin, Gramicidin, Polymyxin B,Tyrothricin und Teixobactin; oder aus der Gruppe der Cytostatika, bestehend aus Cyclophosphamid, Mechlorethamin, Dacarbazine, Nitrosoureas, Temozolomid, Daunorubicin, Epirubicin, Idarubicin, Mitoxantron, Valrubicin, Paclitaxel, Docetaxel, Abraxan, Taxoter, Vorinostat, Romidepsin, Irinotecan, Topotecan, Etoposid, Teniposid, Tafluposid, Bortezomib, Erlotinib, Gefitinib, Imatinib, Vemurafenib, Vismodegib, Azacitidin, Azathioprin, Capecitabin, Cytarabin, Doxifluridin, Fluorouracil, Gemcitabin, Hydroxyurea, Vinblastin, Vincristin, Vindesin und Vinorelbine; oder aus der Gruppe der Virostatika, bestehend aus Ancriviroc, Aplaviroc, Cenicriviroc, Enfuvirtid, Maraviroc, Vicriviroc, Amantadin, Rimantadin, Pleconaril, Idoxuridin, Aciclovir, Brivudin, Famciclovir, Penciclovir, Sorivudin, Valaciclovir, Cidofovir, Brincidofovir, Ganciclovir, Valganciclovir, Foscarnet, Ribavirin, Taribavirin, Filibuvir, Nesbuvir, Sofosbuvir, Tegobuvir, Favipiravir, Abacavir, Didanosin, Elvucitabin, Emtricitabin,Fosalvudintidoxil, Fozivudintidoxil, Stavudin, Zalcitabin, Zidovudin, Lamivudin, Lagociclovir, Tenofovir, Adefovir, Alamifovir, Clevudin, Entecavir, Pradefovir, Telbivudin, Delavirdin, Efavirenz, Emivirin, Etravirin, Lersivirin, Nevirapin, Rilpivirin, Amprenavir, Atazanavir, Brecanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Mozenavir, Nelfinavir, Ritonavir, Saquinavir, Tipranavir, Asunaprevir, Balapiravir, Boceprevir, Ciluprevir, Danoprevir, Daclatasvir, Narlaprevir, Telaprevir, Simeprevir, Vaniprevir, Rupintrivir, Elvitegravir, Dolutegravir, Raltegravir, Fomivirsen, Amenamevir, Bevirimat, Letermovir, Laninamivir, Oseltamivir, Peramivir und Zanamivir. ,

[0015] According to one embodiment of the present invention, the mass of the pharmaceutically active ingredient is at least 5% by weight, based on the total mass of the nanocontainer, preferably at least 10% by weight, particularly preferably at least 15% by weight, and most preferably at least 20% by weight. With the nanocontainer according to the invention, it is even possible, under certain circumstances, to achieve active ingredient loadings per nanoparticle of 70 to 95% by weight, based on the total mass of the nanocontainer. Since the carrier system of the nanocontainer, i.e., the components other than the active ingredient, typically do not have any pharmaceutical efficacy, the nanocontainer according to the invention, due to its design, advantageously allows for a large loading of the active ingredient, thus achieving a very high pharmaceutical efficacy per administered quantity of nanocontainer.

[0016] According to the invention, the term "detection reagent" means a substance or compound that can be detected / located in the body after administration, for example optically via fluorescence in the case of a fluorescent dye, or also by X-ray absorption or magnetic measurements.

[0017] According to one embodiment of the present invention, the detection reagent is selected from the group of fluorescent dyes, for example from Coumarin 6, Lumigen Red, Fluorescein diacetate, Oxonol, Nile Red and Fluorescein isothiocyanate.

[0018] The at least one nonpolar, lipophilic compound is encapsulated in the emulsion of the nanocontainer according to the invention by a biocompatible surfactant. According to the invention, the term "biocompatible" means that the surfactant has no negative impact on living organisms. Biocompatibility can be certified, for example, according to ISO 10993-1-20. According to the invention, the biocompatible surfactant is not subject to any particular restrictions as long as it has at least one polar group (polar, hydrophilic residue) selected from a phosphate group, a sulfate group, a sulfonate group, or a carboxyl group. Furthermore, the surfactant has a nonpolar, hydrophobic residue.

[0019] According to the invention, the emulsion can comprise a single surfactant or a mixture of two or more surfactants. In a preferred embodiment, the surfactant comprises an alkyl phosphate, an alkyl sulfate, an alkyl sulfonate, or an alkyl carboxylate. The alkyl group preferably has 5 to 20 carbon atoms, more preferably 8 to 15 carbon atoms, and most preferably 10 to 12 carbon atoms. In a particularly preferred embodiment, the surfactant comprises sodium or potassium monodecyl phosphate, sodium or potassium dodecyl phosphate, sodium or potassium tocopherol phosphate, sodium or potassium dodecyl sulfate, sodium or potassium laurinate, or sodium or potassium caprinate.

[0020] The nanocontainer according to the invention further comprises an inorganic, biocompatible shell that encloses the emulsion. The at least one polar group of the biocompatible surfactant, which is located in the emulsion and therefore within the shell, is ionically bound (from the inside) to the inorganic, biocompatible shell. Due to its orientation (the nonpolar portion of the surfactant points into the cavity of the shell), the surfactant lipophilizes the cavity of the inorganic shell, thus mechanically stabilizing the emulsion. Since the inorganic, biocompatible shell preferably has a zeta potential of at least -20 mV at pH 7, it ensures high charge stabilization, which advantageously effectively prevents agglomeration in aqueous suspension and simultaneously allows for the redispersal of powders in water or the aerolization of suspension and / or powder.

[0021] According to the claims of the present invention, the inorganic, biocompatible shell comprises a metal phosphate, a metal hydrogen phosphate, a metal dihydrogen phosphate, a metal sulfate, or a metal carbonate, wherein the metal (or the metal cation of the salt) is at least one metal (or metal cation) selected from the group consisting of Zr⁴⁺, ZrO₂⁺, Mg⁺, Ca⁺, Sr⁺, Ba⁺, Cu⁺, Cu⁺, Ag⁺, Zn⁺, Mn⁺, Fe⁺, Fe⁳⁺, Y⁺, and Ln⁳⁺. The metal (or metal cation) is particularly preferably selected from the group consisting of ZrO₂⁺, Mg⁺, Ca⁺, and La⁳⁺.

[0022] According to one embodiment of the present invention, the emulsion forms at least one micelle, wherein in the micelle the surfactant forms a layer around the nonpolar, lipophilic compound and the polar group of the surfactant is ionically bound to the inorganic, biocompatible shell (see Figure 1 According to an alternative embodiment, the emulsion forms two or more micelles, with the surfactant forming a layer around the nonpolar, lipophilic compound in each of the micelles. Each of the at least two micelles is individually enclosed by an inorganic, biocompatible shell, the polar groups of the surfactants in each micelle being ionically bound to the inorganic, biocompatible shell. Furthermore, another inorganic, biocompatible shell encloses the agglomeration of two or more micelles together (see Figure 2 ).

[0023] According to the claims, the nanocontainer according to the invention has a diameter of 10 to 200 nm. If the nanocontainer comprises two or more micelles as in Figure 2 , the respective micelles typically have a diameter of 30 to 100 nm.

[0024] The structure around the nonpolar, lipophilic compound in a specific embodiment of a nanocontainer of the present invention can be described by the general formula [ZrO] 2+< [R( surfactant )OPO 3 ] 2-< @[ZrO] 2+< [HOPO 3 ] 2-< can be described as a core@shell structure, where the R group represents the hydrophobic surfactant group, and the polar phosphate group of the surfactant is ionically incorporated on the inner surface of the zirconyl phosphate shell (see Figure 2 ).

[0025] The present invention further relates to a method according to claim 9 for producing the nanocontainer according to the invention, comprising the steps: (a) Providing an emulsion comprising at least one nonpolar, lipophilic compound and a biocompatible surfactant having at least one polar group selected from a phosphate group, a sulfate group, a sulfonate group, or a carboxyl group; (b) Adding a metal salt wherein the polar groups of the surfactant are stabilized by metal cations of the metal salt to form a sparingly soluble compound; (c) Adding a phosphate salt, a hydrogen phosphate salt, a dihydrogen phosphate salt, a sulfate salt, or a carbonate salt to form an inorganic, biocompatible shell with the metal cations from step (b) such that the inorganic, biocompatible shell comprises the metal phosphate, metal hydrogen phosphate, metal dihydrogen phosphate, metal sulfate, or metal carbonate formed; wherein the inorganic, biocompatible shell encloses the emulsion and the polar group of the biocompatible surfactant is ionically attached to the inorganic, The biocompatible shell is bound, and as a result of its orientation, the surfactant becomes lipophilic within the cavity of the inorganic shell.

[0026] All the above statements regarding the nanocontainer according to the invention also apply to the inventive method for producing the nanocontainer.

[0027] In step (a) of the process according to the invention, an emulsion is provided comprising a nonpolar, lipophilic compound and a biocompatible surfactant having at least one polar group selected from a phosphate group, a sulfate group, a sulfonate group, or a carboxyl group. In the process according to the invention, the biocompatible surfactant acts as a reactant. For example, water, isotonic water, a physiological buffer, an alcohol, or a mixture of several of these solvents can be used as the solvent. Preferred alcohols for use as solvents are methanol, ethanol, propanol, isopropanol, and n-butanol. Furthermore, this aqueous emulsion can optionally also contain lipophilic (auxiliary) solvents, for example, toluene and / or tocopherol.According to another embodiment, the aqueous emulsion can also be free of lipophilic (auxiliary) solvents, which then significantly increases the loading amount of nonpolar, lipophilic compound per nanocontainer compared to aqueous emulsions containing a lipophilic (auxiliary) solvent (by approximately a factor of 10 to 50). According to yet another embodiment, the emulsion can comprise a pharmaceutically active drug and a detection reagent as lipophilic, nonpolar compounds.

[0028] In step (b) of the process according to the invention, a metal salt is added to the emulsion from step (a), whereby the polar groups of the surfactant are stabilized by the metal cations of the metal salt, forming a sparingly soluble compound. The metal salt can be added as a solid, a solution, or a suspension. Preferably, the aforementioned solvents, namely water, isotonic water, alcohols, and mixtures of several of these solvents in which the metal salt is soluble, are also used. The added metal salt (another reactant of the process according to the invention) is thus added to the first reactant, the biocompatible surfactant, not via separate phase systems (polar / nonpolar liquid phase), but in the same (polar) phase system.This results in the formation of a shell (hollow sphere wall) as a sparingly soluble compound through the reaction of the metal cation (in the aqueous dispersion phase) with the biocompatible surfactant. Due to process steps (a) and (b), the biocompatible surfactant is located on the inside of the hollow sphere after the reaction, thus becoming encapsulated (together with the lipophilic active ingredient). The surfactant cannot be separated after the reaction. It is therefore very important that the surfactant is biocompatible.

[0029] In a particularly preferred embodiment of the present invention, water is used as a solvent, in particular water buffered to a pH value of 4 to 8, particularly preferably to a pH value of less than 7.

[0030] The metal cations of the metal salt are selected from Zr⁴⁺, ZrO₂⁺, Mg²⁺, Ca²⁺, Sr²⁺, Ba²⁺, Cu⁺, Cu²⁺, Ag⁺, Zn²⁺, Mn²⁺, Fe²⁺, Fe³⁺, Y³⁺, ​​or Ln³⁺. The anions of the metal salt are not subject to any particular restrictions. Preferably, anions are used that form readily soluble compounds with the metal cations in the solvent used. Suitable metal salts are known to those skilled in the art. Preferably, the halides, nitrates, and sulfates of the aforementioned metals can be used as metal salts. In a particularly preferred embodiment of the present invention, zirconyl chloride is used as the metal salt.

[0031] The hollow sphere wall formed by metal cation-surfactant bonding in step (b) is inherently very thin and therefore not very chemically / mechanically stable. For this reason, the hollow sphere wall is reinforced in step (c). In particular, in step (c) of the process according to the invention, a phosphate salt, a hydrogen phosphate salt, a dihydrogen phosphate salt, a sulfate salt, or a carbonate salt is added to form a (very stable) inorganic, biocompatible shell containing the metal cations from step (b), so that the inorganic, biocompatible shell comprises or is composed of the formed metal phosphate, metal hydrogen phosphate, metal dihydrogen phosphate, metal sulfate, or metal carbonate. The inorganic, biocompatible shell encloses the emulsion, and the polar group of the biocompatible surfactant is ionically bound to the inorganic, biocompatible shell.As a result of its orientation, the surfactant lipophilizes the cavity of the inorganic shell. The order of steps (b) and (c) in the process according to the invention is not fixed, i.e., step (c) can be carried out either before or after step (b) without affecting the resulting nanocontainer.

[0032] The phosphate salt, hydrogen phosphate salt, dihydrogen phosphate salt, sulfate salt, or carbonate salt is added in step (c) as a solid, solution, or suspension. Preferably, the aforementioned solvents, namely water, isotonic water, alcohols, and mixtures of several of these solvents in which the metal salt is soluble, are also used. The salt, a further reactant of the process according to the invention, is thus again supplied exclusively via the dispersion phase (preferably water). In a particularly preferred embodiment of the present invention, water is therefore used as the solvent, in particular water buffered to a pH of 4 to 8, and especially preferably to a pH of less than 7.

[0033] In step (b) and / or step (c), an additive can optionally be added to lower or buffer the pH. Examples of usable additives are organic acids such as citric acid, oxalic acid, tartaric acid, formic acid, acetic acid, etc. According to a preferred embodiment, citric acid is used as the additive, particularly when the polar group of the biocompatible surfactant has a sulfonate or sulfate group.

[0034] The cations of the phosphate salt, hydrogen phosphate salt, dihydrogen phosphate salt, sulfate salt, or carbonate salt are not subject to any particular restrictions. Preferably, metals that lead to readily soluble phosphates, hydrogen phosphates, dihydrogen phosphates, sulfates, or carbonates are used as cations. According to a preferred embodiment, sodium salts are used, in particular sodium dihydrogen phosphate. According to an alternative embodiment, phosphates, hydrogen phosphates, dihydrogen phosphates, sulfates, or carbonates can also be used, which have one or more of the metal cations mentioned for step (b) as cations.

[0035] The reaction temperature of the process according to the invention is not subject to any particular limitation. Preferably, the process is carried out at room temperature.

[0036] After carrying out steps (b) and (c) of the process according to the invention, the resulting (sparingly soluble) nanocontainer precipitates or is suspended in the solvent used. At this point in the process, step (d) can optionally be carried out.

[0037] The optional step (d) of the method according to the invention comprises isolating and / or purifying the precipitated nanocontainer. This isolation and / or purification can be carried out by any suitable method. Such methods are known in the prior art.

[0038] Preferably, the isolation and / or purification of the hybrid compound particles is carried out by a method selected from the group consisting of centrifugation techniques, dialysis techniques, phase transfer techniques, chromatography techniques, ultrafiltration techniques, washing techniques, and combinations thereof. The aforementioned methods for isolating and / or purifying the hybrid compound particles can also be combined and / or carried out multiple times.

[0039] The present invention further relates to the use of the nanocontainer according to the invention, or of the nanocontainer produced by the method according to the invention, in the treatment of infections caused by bacteria and / or viruses or in the treatment of tumors. In particular, the nanocontainer can be used to treat infections caused by bacteria, wherein the bacterium causes tuberculosis or exhibits multi-resistance.

[0040] In summary, the present invention has the following advantages over the prior art: Nanocontainers represent a novel material concept for the delivery of nonpolar, lipophilic compounds such as antibiotics. Preferably, the nanocontainer contains both a pharmaceutically active agent for therapy and a detection reagent, such as a fluorescent dye for diagnostics. Detection of the nanocontainer is possible via simple optical means, for example, through the fluorescence of a contained fluorescent dye anion in cells, tissues, or organs. Detection by X-ray absorption or magnetic measurements is also possible. Synthesis can be achieved through simple precipitation in aqueous solution, as the nanocontainer is sparingly soluble in water. The nanocontainer can contain a wide variety of nonpolar, lipophilic compounds, thus allowing for application in a very broad range of medical therapies.The nonpolar, lipophilic compound is released from the nanocontainer under physiological conditions in a delayed manner, over a period of several hours to several days. This allows for the release of a specific dose of the active ingredient over an extended period and directly at the site of action. Side effects and the undesirable degradation of the active ingredient under physiological conditions, for example in the blood, can be reduced or avoided. The nanocontainer can also contain a wide variety of detection reagents, such as fluorescent dyes. Typically, excitation in the visible light spectrum is achieved using suitable lasers or light-emitting diodes (LEDs), resulting in emission in the visible or infrared range. In addition to the nonpolar, lipophilic compound, the nanocontainer is characterized by non-allergenic and non-toxic components that are completely degraded and excreted under physiological conditions.

[0041] The figures show: Figure 1 An embodiment with a micelle: Encapsulation of lipophilic active ingredients in calcium monododecyl sulfate / calcium hydrogen phosphate nanocontainers, exemplified by filling with BTZ-043 (antibiotic) and Lumigen Red (fluorescent dye), as well as toluene and / or tocopherol as solvents; and Figure 2 An embodiment with multiple micelles: Encapsulation of lipophilic active ingredients in zirconyl monododecyl phosphate@zirconyl hydrogen phosphate nanocontainers using the example of filling with BTZ-043 (antibiotic) and Lumin Red (fluorescent dye) as well as toluene and / or tocopherol as solvents.

[0042] The present invention is further explained by the following non-limiting examples. Examples: Example 1: BTZ-043 in zirconyl monododecyl phosphate @ zirconyl hydrogen phosphate nanocontainers

[0043] 5 mL of deionized water, 500 mg (1.67 mmol) of sodium monododecyl phosphate, 1.1 mL (12.02 mmol) of n-butanol, 0.5 mL (4.72 mmol) of toluene, and 70 mg (0.16 mmol) of BTZ-043 (2-(2-methyl-1,4-dioxa-8-azaspiro(4.5)dec-8-yl)-8-nitro-6-(trifluoromethyl)-4H-1,3-b enzothiazin-4-one) were mixed and 0.1 mL of 1 M hydrochloric acid was added. Vigorous stirring resulted in a transparent, stable emulsion after approximately 10 minutes. 0.5 mL of the emulsion was filtered using a syringe filter and then slowly added dropwise (over 30 minutes) to 20 mL of an aqueous, acetate-buffered solution of 84 mg (0.26 mmol) ZrOCl 2 × 8 H 2 O with a pH of 4.7. The mixture was stirred for one hour and then, while cooling in an ice bath, 3.8 mL (0.38 mmol) of an aqueous 0.1 M NaH 2 PO 4 solution was added dropwise over one hour.The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and subsequently resuspended in 20 mL of deionized water. To determine the particle concentration, 1 mL of the suspension was pipetted twice, transferred to aluminum weighing dishes, and dried in a drying oven at 95 °C for 16 hours. The dry weight was then determined. The average particle concentration was 3.3 mg / mL. Finally, a suspension with a particle concentration of 3.3 mg / mL was prepared by adding Dextran-40 in a 5 wt% aqueous Dextran-40 solution. The drug concentration or loading was determined for suspensions with a particle concentration of 3.3 mg / mL using a UV-VIS calibration curve. The BTZ-043 concentration is therefore 99 µg / mL. Example 2: Bedaquiline in zirconyl monododecyl phosphate@zirconyl hydrogen phosphate nanocontainers

[0044] 5 mL of deionized water, 500 mg (1.67 mmol) of sodium monododecyl phosphate, 1.1 mL (12.02 mmol) of n-butanol, 0.5 mL (4.72 mmol) of toluene, and 48 mg (0.09 mmol) of bedaquiline were mixed and 0.1 mL of 1 M hydrochloric acid was added. Vigorous stirring yielded a transparent, stable emulsion after approximately 10 minutes. 0.5 mL portions of the emulsion were filtered through a syringe filter and then slowly added dropwise (over 30 minutes) to 20 mL portions of an aqueous, acetate-buffered solution of 84 mg (0.26 mmol) of ZrOCl 2 × 8 H₂O at a pH of 4.7. The mixture was stirred for one hour and then, while cooled in an ice bath, 3.8 mL (0.38 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in 20 mL of deionized water.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt% aqueous Dextran-40 solution with a bedaquiline loading of 150 µg / mL. Example 3: Clofazimine in zirconyl monododecyl phosphate @ zirconyl hydrogen phosphate nanocontainers

[0045] 5 mL of deionized water, 500 mg (1.67 mmol) of sodium monododecyl phosphate, 1.1 mL (12.02 mmol) of n-butanol, 0.5 mL (4.72 mmol) of toluene, and 36 mg (0.08 mmol) of clofazimine were mixed and 0.1 mL of 1 M hydrochloric acid was added. Vigorous stirring yielded a transparent, stable emulsion after approximately 10 minutes. 0.5 mL portions of the emulsion were filtered through a syringe filter and then slowly added dropwise (over 30 minutes) to 20 mL portions of an aqueous, acetate-buffered solution of 84 mg (0.26 mmol) of ZrOCl 2 × 8 H₂O at a pH of 4.7. The mixture was stirred for one hour and then, while cooled in an ice bath, 3.8 mL (0.38 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in 20 mL of deionized water.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt% aqueous dextran-40 solution with a clofazimine concentration of 112 µg / mL. Example 4: Lansoprazole in zirconyl monododecyl phosphate @ zirconyl hydrogen phosphate nanocontainers

[0046] 5 mL of deionized water, 500 mg (1.67 mmol) of sodium monododecyl phosphate, 1.1 mL (12.02 mmol) of n-butanol, 0.5 mL (4.72 mmol) of toluene, and 30 mg (0.08 mmol) of lansoprazole were mixed and 0.1 mL of 1 M hydrochloric acid was added. Vigorous stirring yielded a transparent, stable emulsion after approximately 10 minutes. 0.5 mL portions of the emulsion were filtered through a syringe filter and then slowly added dropwise (over 30 minutes) to 20 mL portions of an aqueous, acetate-buffered solution of 84 mg (0.26 mmol) of ZrOCl 2 × 8 H₂O at a pH of 4.7. The mixture was stirred for one hour and then, while cooled in an ice bath, 3.8 mL (0.38 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in 20 mL of deionized water.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt% aqueous Dextran-40 solution with a lansoprazole loading of 155 µg / mL. Example 5: BTZ-043 and luminogen red in zirconyl monododecyl phosphate @ zirconyl hydrogen phosphate nanocontainers

[0047] 5 mL of deionized water, 500 mg (1.67 mmol) of sodium monododecyl phosphate, 1.1 mL (12.02 mmol) of n-butanol, 0.5 mL (4.72 mmol) of toluene, 70 mg (0.16 mmol) of BTZ-043, and 2 mg (1.9 µmol) of Lumigen Red were mixed and 0.1 mL of 1 M hydrochloric acid was added. Vigorous stirring resulted in a transparent, stable emulsion after approximately 10 minutes. 0.5 mL portions of the emulsion were filtered using a syringe filter and then slowly added dropwise (over 30 minutes) to 20 mL portions of an aqueous, acetate-buffered solution of 84 mg (0.26 mmol) of ZrOCl 2 × 8 H₂O at a pH of 4.7. The mixture was stirred for one hour and then, while cooled in an ice bath, 3.8 mL (0.38 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in 20 mL of deionized water.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt% aqueous Dextran-40 solution with a BTZ-043 loading of 99 µg / mL and a Lumigen Rot loading of 3 µg / mL. Example 6: Bedaquiline and luminogen red in zirconyl monododecyl phosphate @ zirconyl hydrogen phosphate nanocontainers

[0048] 5 mL of deionized water, 500 mg (1.67 mmol) of sodium monododecyl phosphate, 1.1 mL (12.02 mmol) of n-butanol, 0.5 mL (4.72 mmol) of toluene, 48 mg (0.09 mmol) of bedaquiline, and 2 mg (1.9 µmol) of luminogen red were mixed and 0.1 mL of 1 M hydrochloric acid was added. Vigorous stirring resulted in a transparent, stable emulsion after approximately 10 minutes. 0.5 mL portions of the emulsion were filtered through a syringe filter and then slowly added dropwise (over 30 minutes) to 20 mL portions of an aqueous, acetate-buffered solution of 84 mg (0.26 mmol) of ZrOCl 2 × 8 H₂O at a pH of 4.7. The mixture was stirred for one hour and then, while cooled in an ice bath, 3.8 mL (0.38 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in 20 mL of deionized water.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt% aqueous Dextran-40 solution with a bedaquiline loading of 144 µg / mL and that for Lumigen Red 3 µg / mL. Example 7: Irinotecan in zirconyl monododecyl phosphate@zirconyl hydrogen phosphate nanocontainers

[0049] 5 mL of deionized water, 500 mg (1.67 mmol) of sodium monododecyl phosphate, 1.1 mL (12.02 mmol) of n-butanol, 0.5 mL (4.72 mmol) of toluene, and 35 mg (0.06 mmol) of irinotecan were mixed and 0.1 mL of 1 M hydrochloric acid was added. Vigorous stirring yielded a transparent, stable emulsion after approximately 10 minutes. 0.5 mL portions of the emulsion were filtered through a syringe filter and then slowly added dropwise (over 30 minutes) to 20 mL portions of an aqueous, acetate-buffered solution of 84 mg (0.26 mmol) of ZrOCl 2 × 8 H₂O at a pH of 4.7. The mixture was stirred for one hour and then, while cooled in an ice bath, 3.8 mL (0.38 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in 20 mL of deionized water.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt% aqueous Dextran-40 solution with an irinotecan loading of 87 µg / mL. Example 8: Paclitaxel in zirconyl monododecyl phosphate @ zirconyl hydrogen phosphate nanocontainers

[0050] 5 mL of deionized water, 500 mg (1.67 mmol) of sodium monododecyl phosphate, 1.1 mL (12.02 mmol) of n-butanol, 0.5 mL (4.72 mmol) of toluene, and 1 mg (1.2 µmol) of paclitaxel were mixed and 0.1 mL of 1 M hydrochloric acid was added. Vigorous stirring yielded a transparent, stable emulsion after approximately 10 minutes. 0.5 mL portions of the emulsion were filtered through a syringe filter and then slowly added dropwise (over 30 minutes) to 20 mL portions of an aqueous, acetate-buffered solution of 84 mg (0.26 mmol) ZrOCl 2 × 8 H₂O with a pH of 4.7. The mixture was stirred for one hour and then, while cooled in an ice bath, 3.8 mL (0.38 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in 20 mL of deionized water.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt% aqueous Dextran-40 solution with a paclitaxel loading of 12 µg / mL. Example 9: BTZ-043 in zirconyl monododecyl phosphate @ zirconyl hydrogen phosphate nanocontainers

[0051] 5 mL of deionized water, 500 mg (1.67 mmol) of sodium monododecyl phosphate, 1.1 mL (12.02 mmol) were added. n-Butanol and 700 mg (1.6 mmol) of BTZ-043 were mixed and treated with 0.1 mL of 1 M hydrochloric acid. Vigorous stirring yielded a transparent, stable emulsion after approximately 10 minutes. 0.5 mL of the emulsion was filtered through a syringe filter and then slowly added dropwise (over 30 minutes) to 20 mL of an aqueous, acetate-buffered solution of 84 mg (0.26 mmol) of ZrOCl 2 × 8 H₂O at a pH of 4.7. The mixture was stirred for one hour, and then, while cooling in an ice bath, 3.8 mL (0.38 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and then resuspended in 20 mL of deionized water. The determination of particle and active ingredient concentrations was carried out as described in Example 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt.The concentration of -% aqueous dextran-40 solution with a BTZ-43 loading is therefore 990 µg / mL. Example 10: Clofazimine in zirconyl monododecyl phosphate @ zirconyl hydrogen phosphate nanocontainers

[0052] 5 mL of deionized water, 500 mg (1.67 mmol) of sodium monododecyl phosphate, 1.1 mL (12.02 mmol) of n-butanol, and 360 mg (0.8 mmol) of clofazimine were mixed and 0.1 mL of 1 M hydrochloric acid was added. Vigorous stirring yielded a transparent, stable emulsion after approximately 10 minutes. 0.5 mL portions of the emulsion were filtered through a syringe filter and then slowly added dropwise (over 30 minutes) to 20 mL portions of an aqueous, acetate-buffered solution of 84 mg (0.26 mmol) ZrOCl 2 × 8 H₂O at a pH of 4.7. The mixture was stirred for one hour and then, while cooled in an ice bath, 3.8 mL (0.38 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in 20 mL of deionized water.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt% aqueous Dextran-40 solution with a clofazimine concentration of 1120 µg / mL. Example 11: Irinotecan in zirconyl monododecyl phosphate@zirconyl hydrogen phosphate nanocontainers

[0053] 5 mL of deionized water, 500 mg (1.67 mmol) of sodium monododecyl phosphate, 1.1 mL (12.02 mmol) of n-butanol, and 350 mg (0.6 mmol) of irinotecan were mixed and 0.1 mL of 1 M hydrochloric acid was added. Vigorous stirring yielded a transparent, stable emulsion after approximately 10 minutes. 0.5 mL portions of the emulsion were filtered through a syringe filter and then slowly added dropwise (over 30 minutes) to 20 mL portions of an aqueous, acetate-buffered solution of 84 mg (0.26 mmol) ZrOCl 2 × 8 H₂O at a pH of 4.7. The mixture was stirred for one hour and then, while cooled in an ice bath, 3.8 mL (0.38 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in 20 mL of deionized water.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt% aqueous Dextran-40 solution with an irinotecan loading of 870 µg / mL. Example 12: BTZ-043 in calcium dodecyl sulfate@calcium hydrogen phosphate nanocontainers

[0054] A yellow, transparent emulsion was obtained by mixing 2.5 ml of distilled water (140 mmol), 700 mg of SDS (2.43 mmol), 0.45 ml of tocopherol (0.43 g, 0.99 mmol), 26 mg (0.07 mmol) of BTZ-043, and 0.45 ml of butanol (0.36 g, 4.91 mmol), resulting in a total volume of 3.25 ml. At the start of the synthesis, 0.2 ml of the previously prepared microemulsion, corresponding to 43 mg of SDS (0.149 mmol, 1 eq.), 1.6 mg (0.004 mmol) of BTZ-043, and 27.6 µl of tocopherol (26.31 mg, 0.0601 mmol), was added to a solution of 221 mg of Na₂HPO₄ (1.24 mmol, 8.3 g). 33 mg of citric acid (0.15 mmol) were added to 50 ml of water. The solution was adjusted to pH 6.1 with 0.5 M NaOH, and 338 mg of calcium acetate (2.13 mmol, 14.2 eq.) were added dropwise to 5 ml of water. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in deionized water.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt% aqueous Dextran-40 solution with a BTZ loading of 40 µg / mL. Example 13: BTZ-043 in calcium dodecyl sulfate@calcium hydrogen phosphate nanocontainers

[0055] A yellow, transparent emulsion was obtained by mixing 2.5 ml of distilled water (140 mmol), 700 mg of SDS (2.43 mmol), 260 mg (0.7 mmol) of BTZ-043, and 0.45 ml of butanol (0.36 g, 4.91 mmol), resulting in a total volume of 3.25 ml. At the start of the synthesis, 0.2 ml of the previously prepared microemulsion, corresponding to 43 mg of SDS (0.149 mmol, 1 eq.) and 16 mg (0.04 mmol) of BTZ-043, was added to a solution of 221 mg of Na₂HPO₄ (1.24 mmol, 8.3 eq.) and 33 mg of citric acid (0.15 mmol) in 50 ml of water. The solution was adjusted to pH 6.1 with 0.5 M NaOH, and 338 mg of calcium acetate (2.13 mmol, 14.2 eq.) was added dropwise in 5 ml of water. The suspension was stirred for a further 20 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in deionized water.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle concentration of 3.3 mg / mL in a 5 wt% aqueous Dextran-40 solution with a BTZ loading of 400 µg / mL. Example 14: BTZ-043 in lanthanum lauryl sulfate / hydrogen phosphate nanocontainers

[0056] A solution of 30 mL deionized water, 15 mg (0.05 mmol) sodium lauryl sulfate, and 90 mg (1.1 mmol) ammonium acetate was prepared and cooled in an ice bath. A solution of 40 mg (0.3 mmol) BTZ043 in 1.2 mL dimethyl sulfoxide (DMSO) was then added with vigorous stirring. During the addition, the liquid phase was further mixed by ultrasonic pulses lasting 10 seconds. Subsequently, 19 mg (0.05 mmol) of LaCl₃ × 7H₂O dissolved in 1.0 mL of water at pH 7.0 was added slowly (over 30 minutes). The mixture was stirred for one hour, and then, while cooling in an ice bath, 0.5 mL (0.1 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 5 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and then resuspended in 10 mL of deionized water. The result is a slightly yellowish suspension.The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle size of around 40 nm and an active ingredient concentration of 4 mg / ml BTZ. Example 15: BTZ-043 in zirconyl monododecyl phosphate / hydrogen phosphate nanocontainers

[0057] A solution of 30 mL deionized water, 25 mg (0.08 mmol) sodium monododecyl phosphate, and 90 mg (1.1 mmol) ammonium acetate was prepared and cooled in an ice bath. A solution containing 40 mg (0.3 mmol) of BTZ043 in 1.2 mL of dimethyl sulfoxide (DMSO) was then added with vigorous stirring. During the addition, the liquid phase was further mixed by ultrasonic pulses lasting 10 seconds. Subsequently, 26 mg (0.08 mmol) of ZrOCl₂·8H₂O dissolved in 1.0 mL of water at pH 7.0 was added slowly (over 30 minutes). The mixture was stirred for one hour, and then, while cooling in an ice bath, 1.0 mL (0.1 mmol) of an aqueous 0.1 M NaH₂PO₄ solution was added dropwise over one hour. The suspension was stirred for a further 5 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and then resuspended in 10 mL of deionized water.The result is a slightly yellowish suspension. The determination of particle and active ingredient concentration was carried out as described in embodiment 1 and yielded a particle size of around 40 nm and an active ingredient concentration of 4 mg / ml BTZ. Example 16: Bedaquiline in zirconyl monododecyl phosphate / hydrogen phosphate nanocontainers

[0058] 3.6 mg sodium monododecyl phosphate (0.01 mmol) was stirred with 2 drops of butanol and 1 ml of deionized water until completely dissolved at 50 °C. 2.5 mg tocopherol phosphate (0.005 mmol) was added and stirred until completely dissolved. A solution of 30 mg ammonium acetate (0.4 mmol) in 5 ml of water was then added, and the resulting mixture was cooled in an ice bath. A solution of 10 mg (0.02 mmol) bedaquiline in 0.4 ml of dimethyl sulfoxide (DMSO) was then injected with vigorous stirring. During the addition, the liquid phase was further mixed by ultrasonic pulses of 10 seconds duration. Subsequently, 3 mg (0.01 mmol) FeCl₃ × 6H₂O dissolved in 1.0 mL of water at pH 7.0 was added slowly (over 30 minutes). The mixture was stirred for one hour and then, while cooling in an ice bath, 0.2 mL (0.02 mmol) of an aqueous 0.1 M NaH 2 PO 4 solution containing 3.9 mg of 3-phosphopropionic acid was added dropwise over one hour.The suspension was stirred for a further 5 hours, then washed twice by repeated centrifugation and resuspension in deionized water, and finally resuspended in 2 mL of deionized water. This resulted in a slightly yellowish suspension. The determination of particle and drug concentrations was carried out as described in Example 1 and yielded a particle size of approximately 20 nm and a drug concentration of 5 mg / ml bedaquiline.

Claims

1. Nanocontainer, comprising an emulsion comprising at least one nonpolar, lipophilic compound encapsulated by a biocompatible surfactant having at least one polar group selected from a phosphate group, a sulfate group, a sulfonate group or a carboxyl group, and an inorganic, biocompatible shell enclosing the emulsion, wherein the inorganic, biocompatible shell comprises a metal phosphate, a metal hydrogen phosphate, a metal dihydrogen phosphate, a metal sulfate, or a metal carbonate, wherein the metal is at least one metal selected from the group consisting of Zr4+, ZrO2+, Mg2+, Ca2+, Sr2+, Ba2+, Cu+, Cu2+, Ag+, Zn2+, Mn2+, Fe2+, Fe3+, Y3+, and Ln3+, preferably a metal selected from the group consisting of ZrO2+, Mg 2+, Ca2+, and La3+, wherein the polar group is ionically bound to the inorganic, biocompatible shell and, as a result of its orientation, the surfactant lipophilizes the cavity of the inorganic shell, wherein the nanocontainer has a diameter of 10 to 200 nm , and wherein at least one nonpolar, lipophilic compound is a pharmaceutically active drug and / or a detection reagent.

2. Nanocontainer according to claim 1, wherein the pharmaceutically active substance or the detection reagent is selected from the group of antibiotics consisting of delamanid, bedaquiline, benzothiazone, amikazin, clofazimine, levofloxacin, ofloxacin, rifampicin, pantoprazole, pyrimethamine, trimethoprim, sulfamethoxazole, sulfadoxine, novobiocin, coumermycin, clorobiocin, metronidazole, norfloxacin, enoxacin, ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, tigecycline, tetracycline, gentamicin, kanamycin, neomycin, netilmicin, streptomycin, tobramycin, chloramphenicol, fusidic acid, cethromycin, narbomycin, telithromycin, lincomycin, daptomycin, dalfopristin, quinupristin, azithromycin, clarithromycin, erythromycin, roxithromycin, linezolid, doxycycline, minocycline, tetracycline, oxytetracycline, tigecycline, imipenem, meropenem, ertapenem, aztreonam, benzylpenicillin, phenoxymethylpenicillin, piperacillin, mezlocillin, ampicillin, amoxicillin, flucloxacillin, methicillin, oxacillin, clavulanic acid, sulbactam, tazobactam, sultamicillin, teicoplanin, vancomycin, bacitracin, colistin, gramicidin, polymyxin B, tyrothricin and teixobactin; or from the group of cytostatic drugs, consisting of cyclophosphamide, mechlorethamine, dacarbazines, nitrosoureas, temozolomide, daunorubicin, epirubicin, idarubicin, mitoxantrone, valrubicin, paclitaxel, docetaxel, abraxan, taxoter, vorinostat, romidepsin, irinotecan, topotecan, etoposide, teniposide, tafluposide, bortezomib, erlotinib, gefitinib, imatinib, vemurafenib, vismodegib, azacitidine, azathioprine, capecitabine, cytarabine, doxifluridine, fluorouracil, gemcitabine, hydroxyurea, vinblastine, vincristine, vindesine, and vinorelbine; or from the group of antivirals, consisting of ancriviroc, aplaviroc, cenicriviroc , enfuvirtide, maraviroc, vicriviroc, amantadine, rimantadine, pleconaril, idoxuridine, acyclovir, brivudine, famciclovir, penciclovir, sorivudine, valaciclovir, cidofovir, brincidofovir, ganciclovir, valganciclovir, foscarnet, ribavirin, taribavirin, filibuvir, nesbuvir, sofosbuvir, tegobuvir, favipiravir, abacavir, didanosine, elvucitabine, emtricitabine, fosalvudintidoxil, fozivudintidoxil, stavudine, zalcitabine, zidovudine, lamivudine, lagociclovir, tenofovir, adefovir, alamifovir, clevudine, entecavir, pradefovir, telbivudine, delavirdine, efavirenz, emivirine, etravirine, lersivirine, nevirapine, rilpivirine, amprenavir, atazanavir, brecanavir, darunavir, fosamprenavir, indinavir, iopinavir, mozenavir, nelfinavir, ritonavir, saquinavir, tipranavir, asunaprevir, balapiravir, oceprevir, ciluprevir, danoprevir, daclatasvir, narlaprevir, telaprevir, simeprevir, vaniprevir, rupintrivir, elvitegravir, dolutegravir, raltegravir, fomivirsen, amenamevir, bevirimat, letermovir, laninamivir, oseltamivir, peramivir and zanamivir; or from the group of fluorescent dyes, consisting of coumarin 6, lumigen red, fluorescein diacetate, oxonol, nile red and fluorescein isothiocyanate.

3. Nanocontainer according to claim 1 or 2, wherein the mass of a pharmaceutically active ingredient is at least 5 wt-%, based on the total mass of the nanocontainer.

4. Nanocontainer according to any one of claims 1 to 3, wherein the surfactant comprises an alkyl phosphate, an alkyl sulfate, an alkyl sulfonate or an alkyl carboxylate .

5. Nanocontainer according to claim 4, wherein the surfactant comprises sodium or potassium monodecyl phosphate, sodium or potassium dodecyl phosphate, sodium or potassium dodecyl sulfate, sodium or potassium laurinate or sodium or potassium caprinate.

6. Nanocontainer according to any one of claims 1 to 5, wherein the inorganic, biocompatible shell has a zeta potential at pH 7 of at least -20 mV.

7. Nanocontainer according to any one of claims 1 to 6, wherein the emulsion forms at least one micelle, wherein in the at least one micelle the surfactant forms a layer around the nonpolar, lipophilic compound and the polar group of the surfactant is ionically bound to the inorganic, biocompatible shell.

8. Nanocontainer according to one of claims 1 to 7, wherein a structure is formed around the nonpolar, lipophilic compound [ZrO]2+[R(surfactant)OPO3]2-, wherein the residue R represents the hydrophobic surfactant residue, and the polar phosphate group of the surfactant is ionically incorporated into the zirconyl phosphate shell.

9. Method for manufacturing a nanocontainer according to any one of claims 1 to 8, comprising the steps: (a) providing an emulsion comprising at least one nonpolar, lipophilic compound and a biocompatible surfactant having at least one polar group selected from a phosphate group, a sulfate group, a sulfonate group or a carboxyl group; (b) adding a metal salt, wherein the polar groups of the surfactant are stabilized by metal cations of the metal salt to form a sparingly soluble compound, wherein the metal is at least a metal selected from the group consisting of Zr4+, ZrO2+, Mg2+, Ca2+, Sr2+, Ba2+, Cu+, Cu2+, Ag+, Zn2+, Mn2+, Fe2+, Fe3+, Y3+, and Ln3+, preferably a metal selected from the group consisting of ZrO2+, Mg2+, Ca2+, and La3+; (c) adding a phosphate salt, a hydrogen phosphate salt, a dihydrogen phosphate salt, a sulfate salt or a carbonate salt to form an inorganic, biocompatible shell with the metal cations from step (b) such that the inorganic, biocompatible shell comprises the metal phosphate, metal hydrogen phosphate, metal dihydrogen phosphate, metal sulfate or metal carbonate formed; wherein the inorganic, biocompatible shell encloses the emulsion and the polar group of the biocompatible surfactant is ionically bound to the inorganic, biocompatible shell, and thereby the surfactant, as a result of its orientation, lipophilizes the cavity of the inorganic shell.

10. Nanocontainer according to any one of claims 1 to 8 for use in the treatment of infections caused by bacteria and / or viruses or for the treatment of tumors.

11. Nanocontainer for use according to claim 10, wherein the bacterium causes tuberculosis or exhibits multi-resistance.