Synergistic transport of lipophyl and hydrophilic active ingredients in nanoparticles

Description

[0001] The present invention relates to nanocontainers for the synergistic transport of lipophilic and hydrophilic active substances or detection reagents. In particular, the nanocontainers according to the invention offer a possibility for the diagnosis and / or treatment of diseases with combinations of active substances (therapy) and detection reagents (diagnostics), which may exhibit different solubility properties. Furthermore, the present invention relates to a method for producing the nanocontainers according to the invention.

[0002] Lipophilic compounds, especially pharmaceutically active substances, 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., intravenous or intraperitoneal administration). Furthermore, the cellular uptake or transport across membranes of lipophilic compounds is often significantly reduced compared to hydrophilic compounds.

[0003] Nanocontainers, or nanoparticles, offer a well-established platform for the delivery of pharmaceutically active agents, such as chemotherapeutic agents for the treatment of cancer. These nanocontainers facilitate the direct and protected delivery of drugs to the tumor, thereby improving the efficacy of the chemotherapeutic agent and / or avoiding potential side effects. In oncology, examples include non-PEGylated liposomal doxorubicin (Myocet®) and PEGylated liposomal doxorubicin (Caelyx®), which demonstrate improved cardiotoxicity, neutropenia, and / or alopecia compared to the free drug. Furthermore, PEGylated liposomal irinotecan (Onivyde®) and nanoparticulate albumin-bound paclitaxel (Abraxane®) enable the use of highly hydrophobic and highly potent taxanes, allowing for higher doses, shorter administration times, and the absence of co-medication.

[0004] Disadvantages of liposomal nanocontainers or nanoparticles include their short half-life and limited stability in suspension. Furthermore, they are expensive to produce, and sterilization is only possible to a limited extent due to their sensitivity to high temperatures and types of radiation.

[0005] Therefore, materials science has proposed further nanoparticle-based concepts for the delivery of chemotherapeutic agents. These concepts are based on organic matrices, such as polymers or biopolymers, or inorganic matrices, such as silicon dioxide, iron oxide, or metal phosphates, in which the pharmaceutical agent is embedded.

[0006] One disadvantage is the presence of toxic components that are difficult to break down under physiological conditions, which can lead to significant side effects. In particular, silicon dioxide has now been shown to have long-term carcinogenic effects.

[0007] Furthermore, the active ingredient is only superficially bound to or within the organic or inorganic matrix. In addition, the amount of active ingredient relative to the total mass of the nanoparticles, with the matrix as the majority component, is usually low (< 20%). Lipophilic active ingredients also exhibit poor stability in suspension, resulting in either excessively rapid or excessively slow release of the active ingredient. Moreover, such matrices offer only limited possibilities for the transport of lipophilic, pharmaceutically active ingredients and for combining different active ingredients. Therefore, despite their complex material composition, such systems are usually only used to treat a single disease. Consequently, studies with organic and inorganic matrices for the transport of pharmaceutically active ingredients have thus far been limited in most cases to [specific applications would be listed here]. in vitro Experiments.

[0008] REIN VIKTOR ET AL: "Zirconyl Hydrogenphosphate Nanocontainers for Flexible Transport and Release of Lipophilic Cytostatics, Insecticides, and Antibiotics", ADVANCED FUNCTIONAL MATERIALS, Vol. 29, No. 28, July 8, 2019, page 1900543, disclose nanocontainers comprising a lipophilic core of a lipophilic pharmaceutical agent and a shell of an inorganic-organic hybrid compound.

[0009] There is therefore a need for new concepts that offer a cost-effective and efficient way to provide lipophilic compounds, such as pharmaceutically active substances or detection reagents, as a combination preparation with hydrophilic compounds, such as pharmaceutically active substances or detection reagents, in order to achieve lower dosages and shorter treatment durations and to avoid side effects.

[0010] The problem described above is solved by the embodiments of the present invention characterized in the claims.

[0011] In particular, according to the invention a nanocontainer is provided comprising a lipophilic core, wherein the lipophilic core comprises at least one lipophilic compound selected from a lipophilic, pharmaceutically active drug or a lipophilic detection reagent; and a hydrophilic shell or shell enclosing the lipophilic core, wherein the hydrophilic shell is composed of an inorganic-organic hybrid compound as an ionic compound, wherein the inorganic-organic hybrid compound consists of an inorganic metal cation selected from Mn²⁺, Sc³⁺, Y³⁺, ​​La³⁺, Fe²⁺, Fe³⁺, [ZrO]²⁺, [HfO]²⁺, Bi³⁺, Gd³⁺, or a lanthanide Ln²⁺ or Ln³⁺, or a hydrated form of these cations (e.g., [Gd(H₂O)ₙ]³⁺ with n = 2-8, [Gd(OH)]²⁺, [GdO]³⁺), and a water-soluble organic drug anion or a water-soluble detection reagent anion, each comprising at least one is composed of a phosphate, phosphonate, sulfate, sulfonate, carbonate or carboxylate group as a functional group.

[0012] As described above, the lipophilic core of the nanocontainer according to the invention is formed or constructed from at least one lipophilic compound, the lipophilic compound being subject to no particular restrictions. According to the invention, the term "lipophilic compound" is understood to mean compounds that are essentially sparingly soluble in water (< 0.1 mol L⁻¹) and readily soluble (> 1.0 mol L⁻¹) in alkanes, for example hexane or dodecane, and / or aromatic hydrocarbons, for example toluene. The lipophilic core can comprise either one or more lipophilic compounds.

[0013] According to the present invention, the at least one lipophilic compound is selected from a lipophilic, pharmaceutically active substance or a lipophilic detection reagent. According to the invention, the term "pharmaceutically active substance" means a substance used as an agent for the treatment or prevention of human or animal diseases, as well as a substance intended for use in or on the human or animal body to restore, improve, or influence bodily functions. According to the invention, the term "detection reagent" means a substance or compound that can be detected / localized in the body after administration, for example, optically via fluorescence in the case of a fluorescent dye, or by X-ray absorption, magnetic measurements, or by means of their radioactive radiation.In particular, the term "detection reagent" does not include surfactants such as monododecyl phosphate. In some cases, a compound can be both the active ingredient and the detection reagent. For example, the chemotherapeutic agent irinotecan itself exhibits blue fluorescence, cytostatic agents of the anthracycline group generally show fluorescence (for example, doxorubicin fluoresces red), and the antiviral drug dolutegravir shows red fluorescence.

[0014] According to the present invention, the lipophilic core is enclosed by a shell based on an inorganic-organic hybrid compound. This structure stabilizes the lipophilic core and makes it available as a transport and storage form.

[0015] The nanocontainers according to the invention do not contain any polymers or polymer compounds that form the core or the shell.

[0016] The shell of the nanocontainer according to the invention comprises, consists of, or is composed of at least one inorganic-organic hybrid compound, which as an ionic compound is in turn composed of an inorganic metal cation and a water-soluble, organic anion, which is an organic active ingredient anion and / or a hydrophilic detection reagent anion.

[0017] According to the present invention, the inorganic metal cation of the hydrophilic shell is selected from the group consisting of Mn²⁺, Sc³⁺, Y³⁺, ​​La³⁺, Fe²⁺, Fe³⁺, [ZrO]²⁺, [HfO]²⁺, Bi³⁺, Gd³⁺, or a lanthanide Ln²⁺ or Ln³⁺, or a hydrated form of these cations (e.g., [Gd(H₂O)ₙ]³⁺ with n = 2-8, [Gd(OH)]²⁺, [GdO]²⁺), or mixtures thereof. The inorganic cation selected from the group consisting of Gd³⁺, [Gd(OH)]²⁺, [GdO]²⁺, and [ZrO]²⁺ is particularly preferred.

[0018] By selecting specific metal cations from the list defined above, the nanocontainer can be equipped with additional properties. In particular, by selecting heavy, magnetic, and / or radioactive inorganic metal cations, for example [ZrO]²⁺, [89ZrO]²⁺, [225Ac³⁺, [HfO]²⁺, Bi³⁺, Gd³⁺, or Mn²⁺, the nanocontainers can be detected by X-ray absorption, magnetic measurements, and / or radioactive decay.

[0019] According to the present invention, the inorganic-organic hybrid compound is an ionic compound comprising a hydrophilic organic drug anion or a hydrophilic detection reagent anion. The definitions of "drug anion" and "detection reagent anion" correspond to the aforementioned definitions of "pharmaceutically active drug" and "detection reagent".

[0020] Furthermore, the water-soluble organic active ingredient anion or the water-soluble detection reagent anion each contains at least one phosphate, phosphonate, sulfate, sulfonate, carbonate, or carboxylate group as a functional group in order to combine with the inorganic metal cation to form the inorganic-organic hybrid compound as an ionic compound, which forms the shell surrounding the lipophilic core of the nanocontainers according to the invention. The inorganic-organic hybrid compound itself is sparingly soluble in water.

[0021] According to a preferred embodiment of the present invention, the at least one lipophilic, pharmaceutically active ingredient is selected from the group of antibiotics consisting of delamanid, bedaquiline, benzothiazinones such as benzothiazinon 043, clofazimine, rifampicin, levofloxacin, cefaclor, cefpodoxime, imipenem, meropenem, ciprofloxacin, levofloxacin, norfloxacin, chloramphenicol, trimethoprim, azithromycin, metronidazole, linezolid, tyrothricin, rifabutin, rifaximin, fusidic acid, doxycycline, hydroxytamoxifen and pantoprazole; or the group of antivirals consisting of amantadine, rimantadine, penciclovir, emivirine, FGI-106, maraviroc, sofosbuvir, baloxavirmarboxil, etravirine, nevirapine, atazanavir, indinavir, lopinavir, nelfinavir, tipranavir, boceprevir, telaprevir, dolutegravir, raltegravir and tecovirimat;or the group of chemotherapeutic agents consisting of ifosfamide, paclitaxel, docetaxel, Abraxan, Taxoter, mechlorethamine, erlotinib, gefitinib, imatinib, vemurafenib, cisplatin, daunorubicin, epirubicin, lomustine, vismodegib, actinomycin D, vinorelbine, camptothecin, topotecan, irinotecan, etoposide, teniposide, and mercaptopurine; or the group of anti-inflammatory drugs consisting of cannabidiol, triamcinolone, budesonide, diclofenac, cortisol, calcitriol, leflunomide, and nonsteroidal anti-inflammatory drugs.

[0022] Furthermore, according to a further preferred embodiment of the present invention, the detection reagent is selected from the group of fluorescent dyes consisting of Lumigen Red, Lumigen Orange, Lumigen Yellow or Lumigen Green, magnesium phthalocyanine, zinc phthalocyanine, 1,1'-diethyl-4,4'-carbocyanini iodide, 3,3'-diethylthiadicarbocyanini iodide, magnesium tetraphenylporphyrin and phthalocyanine.

[0023] According to a preferred embodiment of the present invention, the mass of the lipophilic, pharmaceutically active ingredient and / or the lipophilic detection reagent is 50 to 100 wt.%, based on the total mass of the lipophilic core, preferably at least 60 wt.%, particularly preferably at least 70 wt.%, and most preferably at least 75 wt.%. Since the carrier system of the nanocontainer, i.e., the components other than the active ingredient, typically have no pharmaceutical effect, a large loading quantity of active ingredient can be achieved with the nanocontainer according to the invention, so that a very high pharmaceutical efficacy per administered nanocontainer quantity can be attained.

[0024] According to one embodiment of the present invention, the mass of the lipophilic, pharmaceutically active ingredient is less than 100% by weight when the lipophilic core comprises one or more lipophilic excipients.

[0025] Lipophilic excipients are compounds that have a beneficial effect on the properties of the lipophilic core. An example is α-tocopherol, which has antioxidant properties and can thus lead to improved stability. Other lipophilic excipients include toluene, phellandrene, or natural oils such as oleic acid or linolenic acid.

[0026] According to one embodiment of the present invention, the lipophilic core has a diameter of 10 to 150 nm, measured by electron microscopy. Preferably, the lipophilic core has a diameter of at least 10 nm, more preferably at least 20 nm, and most preferably at least 30 nm. A diameter below the aforementioned minimum is technically difficult to achieve.

[0027] The lipophilic core more preferably has a diameter of at most 120 nm, more preferably of at most 80 nm and most preferably of at most 50 nm.

[0028] As explained above, the shell of the nanocontainer is formed from an inorganic-organic hybrid compound. This inorganic-organic hybrid compound consists of a metal cation and either a hydrophilic organic drug anion or a hydrophilic detection reagent anion.

[0029] According to the present invention, the hydrophilic drug anion or the hydrophilic detection reagent anion is selected from the group of antibiotics consisting of clindamycin phosphate, erythromycin phosphate, tedizolid phosphate, CpG oligodeoxynucleotides, fosfomycin, moxalactam, ceftriaxone, amoxicillin, phenoxymethylpenicillin, aztreonam, moxifloxacin and bacitracin; or the group of antiviral drugs consisting of idoxuridine phosphate, aciclovir phosphate, penciclovir phosphate, ganciclovir phosphate, remdesivir phosphate, glidesivir phosphate, vidarabine phosphate, ribavirin phosphate, abacavir phosphate, stavudine phosphate, adefovir, fosamprenavir, fostemsavir, tenofovir, brincidofovir, cidofovir, foscarnet, ivermectin, bevirimat and zanamivir, or the group of chemotherapeutic agents consisting of 5-fluoro-2'-deoxyuridine 5'-monophosphate, gemcitabine monophosphate, gemcitabine triphosphate, fludarabine, pemetrexed, methotrexate, estramustine phosphate, streptozotocin phosphate, mitoxantrone phosphate, azacitidine phosphate, cyclophosphamide Mustard, SN-38, melphalan, chlorambucil and bendamustine;or the group of anti-inflammatory drugs consisting of betamethasone phosphate, dexamethasone phosphate, prednisolone phosphate, sulfasalazine, acetylsalicylate, methotrexate, ibuprofen, naproxen, and ketoprofen; or the group of fluorescent dyes consisting of phenyllumbelliferone phosphate, flavin mononucleotide, methylfluorescine phosphate, resorufin phosphate, Dynomics 546-uridine triphosphate, Dynomics 647-uridine triphosphate, Amaranth Red, Chicago Sky Blue, Direct Blue 71, Congo Red, Nuclear Fast Red, Acid Red 97, and Evans Blue.

[0030] The compounds listed above exist as anions. The commonly used active ingredient names are employed, i.e., clindamycin phosphate (although the starting compound is not the anion, but the acid or the sodium salt), ibuprofen (correct as the starting compound; however, the active ingredient in the nanoparticles is the anion), etc. It is known to those skilled in the art that the corresponding anion is formed, or can be formed, by dissolving the acid or the sodium salt in water.

[0031] In the case of SN-38, which in itself does not have any of the functional groups defined according to the invention, the aqueous solution thereof must be made alkaline so that the inner cyclic ester opens and a free carboxyl function is formed.

[0032] According to one embodiment of the present invention, the mass of the hydrophilic, pharmaceutically active agent and / or the detection reagent is 50 to 90 wt.%, based on the total mass of organic anions in the tray, preferably at least 60 wt.%, particularly preferably at least 70 wt.%, and most preferably at least 75 wt.%. Since the carrier system of the nanocontainer, i.e., the components other than the active ingredient, typically have no pharmaceutical effect, a large loading quantity of active ingredient can be achieved with the nanocontainer according to the invention, so that a very high pharmaceutical efficacy per administered nanocontainer quantity can be attained.

[0033] For example, if a lipophilic, pharmaceutically active substance is used in the core and a (hydrophilic) detection reagent is used in the shell or casing, the nanocontainer according to the invention can advantageously release the active substance after administration and be localized by the detection reagent in, for example, cells, tissues and organs.

[0034] According to a further embodiment of the present invention, the nanocontainer has a diameter of 20 to 300 nm, measured by electron microscopy. Particularly preferably, the nanocontainer has a diameter of 30 nm or more, and most preferably 50 nm or more. If the diameter of the nanocontainer is above the aforementioned lower limit, the nanocontainer exhibits advantageous stability and a sufficient amount of active ingredient per nanocontainer.

[0035] The nanocontainer preferably has a diameter of 250 nm or less, more preferably of 150 nm or less, and most preferably of 100 nm or less.

[0036] Another aspect of the present invention relates to a method for producing such nanocontainers. The production of the core-shell particles is carried out essentially by the solvent-antisolvens method (see Figure 2In this process, a highly concentrated, preferably saturated solution of the lipophilic active ingredient or detection reagent is first prepared in a suitable solvent. This solvent solution is injected as rapidly as possible into a polar antisolvene under vigorous stirring and / or intensive ultrasonic mixing. Preferably, this is water or a mixture of water with other water-miscible solvents. A prerequisite is that the active ingredient dissolves very well in the solvent but very poorly in the antisolvene. Furthermore, the solvent must be miscible with the antisolvene, at least within a certain concentration range. The injection of the solvent solution into the antisolvene then leads to the precipitation of the lipophilic active ingredient or detection reagent, forming nanoparticles. Subsequently, a marker is applied to the nanoparticles, which consist of the lipophilic active ingredient or detection reagent.Detection reagent, the shell is deposited based on the inorganic-organic hybrid compound (see . Figure 2 The organic functional anion is usually added first. The solution containing the inorganic cation is then slowly added dropwise, causing the inorganic-organic hybrid compound to slowly deposit onto and coat the lipophilic particle core. If necessary, intermediate layers (e.g., surfactants such as tocopherol phosphate or monododecyl phosphate) can be used to increase and improve the adhesion and deposition of the hydrophilic hybrid compound onto the lipophilic particle core.

[0037] All the above statements regarding the nanocontainer according to the invention also apply to the inventive method for producing the nanocontainer.

[0038] In step (I) of the process according to the invention, a solution of the at least one lipophilic compound, wherein the lipophilic compound is a lipophilic, pharmaceutically active agent and / or a lipophilic detection reagent, is provided. For example, methanol, ethanol, 1-propanol, 2-propanol, butanol, tetrahydrofuran, dioxane, benzyl alcohol, dimethyl sulfoxide, acetonitrile, dimethylformamide, acetone, hexane, dodecane, toluene, or mixtures thereof can be used as a solvent. Preferred solvents are ethanol, benzyl alcohol, acetone, tetrahydrofuran, and dimethyl sulfoxide.

[0039] According to a further embodiment, the solution of the at least one lipophilic compound can also contain a lipophilic excipient, for example tocopherol phosphate or monodecyl phosphate. The lipophilic excipient can increase the stability of the lipophilic core. If no lipophilic excipient is added, the loading amount of lipophilic compound per nanocontainer increases considerably.

[0040] In step (II) of the process according to the invention, the solution provided in step (I) is then injected into a polar solvent. Examples of suitable polar solvents include deionized water, aqueous NaCl solutions, ethanol, dimethyl sulfoxide, or mixtures thereof. Deionized water or aqueous NaCl solutions are preferred solvents.

[0041] According to a further embodiment of the present invention, the lipophilic excipient need not be contained in the solution provided in step (I). Optionally, one or more lipophilic excipients can also be provided in the polar solvent.

[0042] Furthermore, one or more chemical compounds, such as ionic compounds, may be present in the polar solvent. Ammonium acetate, which stabilizes the pH of the polar solvent, can be mentioned as an example.

[0043] In step (III), the organic anion and the inorganic cation, which form the inorganic-organic hybrid compound for the construction of the shell, are then added one after the other, usually in this order.

[0044] The reaction temperature of the process according to the invention is not subject to any particular limitation. Typically, a temperature range between -50°C and +90°C is used. Cooling with ice or dry ice or a suitable cooling liquid (e.g., cooling with a cryostat) can be advantageous to reduce the solubility of the substances. Preferably, the process is carried out at room temperature.

[0045] After step (III) is carried out, the nanocontainer formed according to the invention typically precipitates or is present in suspension in the solvent used. Step (IV) can optionally be carried out after step (III). This optional step (IV) comprises isolating and / or purifying the precipitated nanocontainer. This isolation and / or purification is not subject to any restrictions and can be carried out by any suitable method. Such methods are known in the prior art.

[0046] Preferably, the isolation and / or purification of the nanocontainers is carried out by a method selected from the group consisting of centrifugation techniques, dialysis techniques, phase transfer techniques, chromatography techniques, washing techniques, and combinations thereof. The aforementioned methods can also be combined and / or performed multiple times.

[0047] Another aspect of the present invention relates to a nanoparticle comprising the nanocontainer according to the invention, functionalized with at least one element selected from the group consisting of antibodies, peptides, 5-aminolevulinic acid, folic acid derivatives, albumin derivatives, saccharides, and ligands for specific binding to cell receptors. This enables targeted transport of the nanocontainer and targeted release of the active substances or detection reagents.

[0048] Another aspect of the present invention relates to the nanocontainer for use in the treatment of infections caused by bacteria and / or viruses, inflammatory autoimmune reactions or for the treatment of tumors.

[0049] The figures show: Fig. 1 Figure 1 shows the structure of the core@shell nanocontainer according to the invention, with a lipophilic active ingredient as the core and an inorganic-organic hybrid compound as the shell. Fig. 2 Figure 1 shows the synthesis of core@shell nanocontainers according to the invention with the formation of the lipophilic core and the hydrophilic shell using the example of CBD@[ZrO] 2+< [FMN] 2-< , wherein CBD: cannabidiol forms the core and FMN: flavin mononuclide forms the shell. Fig. 3Figure 2 shows microscopy images according to the following embodiment 2, which illustrates the internalization of the nucleus-shell nanocontainers by pancreatic tumor cells. 25,000 cells (13,000 cells / cm²) were plated onto coverslips. After 24 h, the cells were treated with the ITC@[ZrO]²⁺[FLU]²⁻ nucleus-shell nanocontainers and the reference nanocontainers (50 µL / 500 µL medium) for 48 h, counterstained with DAPI (nuclei staining), fixed, and analyzed under a confocal fluorescence microscope. Figure 2 shows a close-up at 63x magnification; the nanocontainers (of the DUT-546 dye) are shown in the light areas, the dark areas show the DAPI-stained nuclei. Figure 3 shows an overview image (10x magnification) showing DAPI-stained nuclei. The toxic effect of the ITC@[ZrO] 2+< [FLU] 2-< -core@shell nanocontainers (hardly any cells present) compared to the reference nanocontainers (a confluent carpet of cells) is significant. Fig. 4Figure 3 shows diagrams according to the following embodiment, wherein 10,000 breast cancer cells (pH8N8) were plated with a concentration of 30,000 cells / cm² and treated with increasing concentrations of the ITC@[ZrO]²⁺<[FLU]²⁻-core@shell nanocontainers and the reference nanocontainers, which do not contain any pharmaceutically active substance. The efficacy in inhibiting cell growth was measured using the CellTiter 96® AQueous One Solution Cell Proliferation Assay before (2 h) and after treatment (24 h). The experiment was performed as a triplicate; the bars represent the means and the error bars the standard deviations. Examples

[0050] The following examples serve to illustrate the present invention, but are not limited to it. Example 1.1: Production of CBD@[ZrO] 2+< [FMN] 2-< - nanocontainers:

[0051] Tocopherol phosphate (disodium salt; 3.8 mg, 7.0 µmol) and ammonium acetate (36.1 mg, 468 µmol) are each dissolved in 6 mL of deionized water. Both solutions are combined and cooled in an ice bath. A solution of cannabidiol (CBD; 2.3 mg, 7.2 µmol) in 0.2 mL of ethanol is injected with vigorous stirring. During and after injection, the solution / suspension is further mixed using a 10-second ultrasonic pulse. The resulting suspension containing CBD nanoparticles, which will form the nanocontainer core, remains colloidally stable for approximately 1 hour.

[0052] In the next step, the CBD nanoparticle suspension is added dropwise over 2 minutes to 9 mL of a ZrOCl₂ solution (octahydrate; 6.8 mg, 37.9 µmol) with intensive stirring. This suspension is stirred for a further 10 minutes. The mixture is then centrifuged (10 minutes, 13,000 rpm). The nanoparticles are then resuspended in 6 mL of the ammonium acetate solution described above using an ultrasonic probe (1 minute) or by intensive stirring. After 30 seconds, 5 mL of a flavin mononucleotide solution (FMN, disodium salt; 3.2 mg, 7.0 µmol) are added over a period of 10 seconds and stirred for a further 10 minutes. In this way, [ZrO] 2+< [FMN] 2-< is deposited as an inorganic-organic hybrid compound as a shell on the CBD core, so that CBD@[ZrO] 2+< [FMN] 2-< -core@shell nanocontainers are formed.The resulting yellow suspension is centrifuged (10 min, 25000 rpm min -1< ), and the CBD@[ZrO] 2+< [FMN] 2-< -core@shell nanocontainers are resuspended in deionized water.

[0053] The CBD@[ZrO] 2+< [FMN] 2-< core@shell nanocontainers containing an anti-inflammatory agent and a fluorescent dye are highly stable as a colloidal suspension in water. Electron microscopy reveals an average diameter of 50 nm, with the core having a diameter of approximately 20 nm and the shell a thickness of about 15 nm. Example 1.2: Production of ERB@[ZrO] 2+< [FdUMP] 2-< -nanocontainers:

[0054] Tocopherol phosphate (disodium salt; 3.8 mg, 7.0 µmol) and ammonium acetate (36.1 mg, 468 µmol) are each dissolved in 6 mL of deionized water. Both solutions are combined and cooled in an ice bath. A solution of epirubicin (ERB; 3.9 mg, 7.2 µmol) in 0.2 mL of ethanol is injected with vigorous stirring. During and after injection, the solution / suspension is further mixed using a 10-second ultrasonic pulse. The resulting suspension containing ERB nanoparticles, which will form the nanocontainer core, remains colloidally stable for approximately 1 hour.

[0055] In the next step, the ERB nanoparticle suspension is added dropwise over 2 minutes to 9 mL of a ZrOCl₂ solution (octahydrate; 6.8 mg, 37.9 µmol) with intensive stirring. This suspension is stirred for a further 10 minutes. The mixture is then centrifuged (10 minutes, 13,000 rpm). The nanoparticles are then resuspended in 6 mL of the ammonium acetate solution described above using an ultrasonic probe (1 minute) or by intensive stirring. After 30 seconds, 5 mL of a 5-fluoro-2'-deoxyuridine-5'-monophosphate solution (FdUMP, disodium salt; 2.3 mg, 7.0 µmol) are added over a period of 10 seconds and stirred for a further 10 minutes. In this way, [ZrO] 2+< [FdUMP] 2-< is deposited as an inorganic-organic hybrid compound as a shell on the ERB core, so that ERB@[ZrO] 2+< [FdUMP] 2-< -core@shell nanocontainers are formed.The resulting suspension is centrifuged (10 min, 25000 rpm min -1< ), and the ERB@[ZrO] 2+< [FdUMP] 2-< -core@shell nanocontainers are resuspended in deionized water.

[0056] The ERB@[ZrO] 2+< [FdUMP] 2-< core@shell nanocontainers containing two chemotherapeutic agents are very stable as a colloidal suspension in water. Electron microscopy reveals a mean diameter of approximately 60 nm, with the core having a mean diameter of approximately 30 nm and the shell having a thickness of approximately 15 nm.

[0057] The nanocontainer core and / or nanocontainer shell can be fluorescently labeled by adding Lumigen Red to the ERB solution (1 mol% based on the amount of ERB) and / or Dynomics-647-uridine triphosphate to the FdUMP solution (0.1 mol% based on the amount of FdUMP). The absorption and emission behavior of the respective fluorescent dyes is known to those skilled in the art. Example 1.3: Production of PAC@[Gd(OH)] 2+< [GemP] 2-< -nanocontainers:

[0058] Tocopherol phosphate (disodium salt; 3.8 mg, 7.0 µmol) and ammonium acetate (36.1 mg, 468 µmol) are each dissolved in 6 mL of deionized water. Both solutions are combined and cooled in an ice bath. A solution of paclitaxel (PAC; 6.1 mg, 7.2 µmol) in 0.2 mL of tetrahydrofuran is injected with vigorous stirring. During and after injection, the solution / suspension is further mixed using a 10-second ultrasonic pulse. The resulting suspension containing PAC nanoparticles, which will form the nanocontainer core, remains colloidally stable for approximately 1 hour.

[0059] In the next step, the suspension of PAC nanoparticles is added dropwise over 2 minutes to 9 mL of a GdCl₃ solution (hexahydrate; 14.1 mg, 37.9 µmol) with intensive stirring. This suspension is stirred for a further 10 minutes. The mixture is then centrifuged (10 minutes, 13,000 rpm). The nanoparticles are then resuspended in 6 mL of the ammonium acetate solution described above using an ultrasonic probe (1 minute) or by intensive stirring. After 30 seconds, 5 mL of a gemcitabine monophosphate solution (GemP, disodium salt; 2.4 mg, 7.0 µmol) are added over a period of 10 seconds and stirred for a further 10 minutes. In this way, [Gd(OH)] 2+< [GemP] 2-< is deposited as an inorganic-organic hybrid compound as a shell on the PAC core, so that PAC@[Gd(OH)] 2+< [GemP] 2-< -core@shell nanocontainers are formed.The resulting suspension is centrifuged (10 min, 25000 rpm min -1< ), and the PAC@[Gd(OH)] 2+< [GemP] 2-< -core@shell nanocontainers are resuspended in deionized water.

[0060] The PAC@[Gd(OH)] 2+< [GemP] 2-< -core@shell nanocontainers containing two chemotherapeutic agents are very stable as a colloidal suspension in water. Electron microscopy reveals a mean diameter of approximately 50 nm, with the core having a mean diameter of approximately 20 nm and the shell having a thickness of approximately 15 nm.

[0061] The nanocontainer core and / or nanocontainer shell can be fluorescently labeled by adding Lumigen Green to the PAC solution (1 mol% based on the amount of PAC) and / or Dynomics-647-uridine triphosphate to the GemP solution (0.1 mol% based on the amount of GemP). The absorption and emission behavior of the respective fluorescent dyes is known to those skilled in the art. Example 1.4: Production of AMT@[ZrO] 2+< [RemP] 2-< -nanocontainers:

[0062] Tocopherol phosphate (disodium salt; 3.8 mg, 7.0 µmol) and ammonium acetate (36.1 mg, 468 µmol) are each dissolved in 6 mL of deionized water. Both solutions are combined and cooled in an ice bath. A solution of amantadine (AMT; 1.1 mg, 7.2 µmol) in 0.4 mL of tetrahydrofuran is injected with vigorous stirring. During and after injection, the solution / suspension is further mixed using a 10-second ultrasonic pulse. The resulting suspension containing AMT nanoparticles, which will form the nanocontainer core, remains colloidally stable for approximately 1 hour.

[0063] In the next step, the suspension of AMT nanoparticles is added dropwise over 2 minutes to 9 mL of a ZrOCl₂ solution (octahydrate; 6.8 mg, 37.9 µmol) with intensive stirring. This suspension is stirred for a further 10 minutes. The mixture is then centrifuged (10 minutes, 13,000 rpm). The nanoparticles are then resuspended in 6 mL of the ammonium acetate solution described above using an ultrasonic probe (1 minute) or by intensive stirring. After 30 seconds, 5 mL of a remdesivir phosphate solution (RemP, disodium salt; 2.6 mg, 7.0 µmol) are added over a period of 10 seconds and stirred for a further 10 minutes. In this way, [ZrO]²⁺< [RemP]²⁻< is deposited as an inorganic-organic hybrid compound as a shell on the AMT core, so that AMT@[ZrO]²⁺< [RemP]²⁻< core@shell nanocontainers are formed. The resulting suspension is centrifuged (10 min, 25,000 rpm) and the AMT@[ZrO]²⁺< [RemP]²⁻< core@shell nanocontainers are resuspended in deionized water.

[0064] The AMT@[ZrO] 2+< [RemP] 2-< -core@shell nanocontainers containing two antiviral agents are very stable as a colloidal suspension in water. Electron microscopy reveals a mean diameter of approximately 40 nm, with the core having a mean diameter of approximately 20 nm and the shell having a thickness of approximately 10 nm.

[0065] The nanocontainer core and / or nanocontainer shell can be fluorescently labeled by adding Lumigen Orange to the AMT solution (1 mol% based on the amount of AMT) and / or Dynomics-546-uridine triphosphate to the RemP solution (0.1 mol% based on the amount of RemP). The absorption and emission behavior of the respective fluorescent dyes is known to those skilled in the art. Example 1.5: Production of ERB@[ZrO] 2+< [FdUMP] 2-< -nanocontainers:

[0066] Tocopherol phosphate (disodium salt; 1.9 mg, 3.5 µmol) and ammonium acetate (36.1 mg, 468 µmol) are each dissolved in 6 mL of deionized water. Both solutions are combined and cooled in an ice bath. A solution of epirubicin (ERB; 7.8 mg, 14.4 µmol) in 0.4 mL of ethanol is injected with vigorous stirring. During and after injection, the solution / suspension is further mixed using a 10-second ultrasonic pulse. The resulting suspension containing ERB nanoparticles, which will form the nanocontainer core, remains colloidally stable for approximately 1 hour.

[0067] In the next step, the ERB nanoparticle suspension is added dropwise over 2 minutes to 9 mL of a ZrOCl₂ solution (octahydrate; 6.8 mg, 37.9 µmol) with intensive stirring. This suspension is stirred for a further 10 minutes. The mixture is then centrifuged (10 minutes, 13,000 rpm). The nanoparticles are then resuspended in 6 mL of the ammonium acetate solution described above using an ultrasonic probe (1 minute) or by intensive stirring. After 30 seconds, 5 mL of a 5-fluoro-2'-deoxyuridine-5'-monophosphate solution (FdUMP, disodium salt; 4.5 mg, 14.0 µmol) are added over a period of 10 seconds and stirred for a further 10 minutes. In this way, [ZrO] 2+< [FdUMP] 2-< is deposited as an inorganic-organic hybrid compound as a shell on the ERB core, so that ERB@[ZrO] 2+< [FdUMP] 2-< -core@shell nanocontainers are formed.The resulting suspension is centrifuged (10 min, 25000 rpm min -1< ), and the ERB@[ZrO] 2+< [FdUMP] 2-< -core@shell nanocontainers are resuspended in deionized water.

[0068] The ERB@[ZrO] 2+< [FdUMP] 2-< core@shell nanocontainers containing two chemotherapeutic agents are very stable as a colloidal suspension in water. Electron microscopy reveals a mean diameter of approximately 80 nm, with the core having a mean diameter of approximately 40 nm and the shell having a thickness of approximately 20 nm.

[0069] The nanocontainer core and / or nanocontainer shell can be fluorescently labeled by adding Lumigen Red to the ERB solution (1 mol% based on the amount of ERB) and / or Dynomics-647-uridine triphosphate to the FdUMP solution (0.1 mol% based on the amount of FdUMP). The absorption and emission behavior of the respective fluorescent dyes is known to those skilled in the art. Example 1.6: Production of DCF@[Gd(OH)] 2+< [BMP] 2-< -nanocontainers:

[0070] Tocopherol phosphate (disodium salt; 3.8 mg, 7.0 µmol) and ammonium acetate (36.1 mg, 468 µmol) are each dissolved in 6 mL of deionized water. Both solutions are combined and cooled in an ice bath. A solution of diclofenac (DCF, sodium salt; 2.3 mg, 7.2 µmol) in 0.2 mL of benzyl alcohol is injected with vigorous stirring. During and after injection, the solution / suspension is further mixed using a 10-second ultrasonic pulse. The resulting suspension containing DCF nanoparticles, which will form the nanocontainer core, remains colloidally stable for approximately 1 hour.

[0071] In the next step, the DCF nanoparticle suspension is added dropwise over 2 minutes to 9 mL of a GdCl₃ solution (hexahydrate; 14.1 mg, 37.9 µmol) with intensive stirring. This suspension is stirred for a further 10 minutes. The mixture is then centrifuged (10 minutes, 13,000 rpm). The nanoparticles are then resuspended in 6 mL of the ammonium acetate solution described above using an ultrasonic probe (1 minute) or by intensive stirring. After 30 seconds, 5 mL of a betamethasone phosphate solution (BMP, disodium salt; 3.6 mg, 7.0 µmol) are added over 10 seconds and stirred for a further 10 minutes. In this way, [Gd(OH)] 2+< [BMP] 2-< is deposited as an inorganic-organic hybrid compound as a shell on the DCF core, so that DCF@[Gd(OH)] 2+< [BMP] 2-< -core@shell nanocontainers are formed.The resulting suspension is centrifuged (10 min, 25000 rpm min -1< ), and the DCF@[Gd(OH)] 2+< [BMP] 2-< -core@shell nanocontainers are resuspended in deionized water.

[0072] The DCF@[Gd(OH)] 2+< [BMP] 2-< core@shell nanocontainers containing two anti-inflammatory agents are very stable as a colloidal suspension in water. Electron microscopy reveals a mean diameter of approximately 50 nm, with the core having a mean diameter of approximately 20 nm and the shell having a thickness of approximately 15 nm.

[0073] The nanocontainer core and / or nanocontainer shell can be fluorescently labeled by adding 3,3-diethylthiadicarbocyaniniodide to the DCF solution (1 mol% based on the amount of DCF) and / or adding flavin mononuclide to the BMP solution (5.0 mol% based on the amount of BMP). The absorption and emission behavior of the respective fluorescent dyes is known to those skilled in the art. Example 1.7: Production of BDQ@[ZrO] 2+< [CLP] 2-< -nanocontainers:

[0074] Tocopherol phosphate (disodium salt; 3.8 mg, 7.0 µmol) and ammonium acetate (36.1 mg, 468 µmol) are each dissolved in 6 mL of deionized water. Both solutions are combined and cooled with an ice bath. A solution of bedaquiline (BDQ; 4.0 mg, 7.2 µmol) in 0.3 mL of dimethyl sulfoxide is injected with vigorous stirring.

[0075] During and after injection, the solution / suspension is further mixed using a 10-second ultrasonic pulse. The resulting suspension containing BDQ nanoparticles, which will form the nanocontainer core, remains colloidally stable for approximately 1 hour.

[0076] In the next step, the suspension of BDQ nanoparticles is added dropwise over 2 minutes to 9 mL of a ZrOCl₂ solution (octahydrate; 6.8 mg, 37.9 µmol) with intensive stirring. This suspension is stirred for a further 10 minutes. The mixture is then centrifuged (10 minutes, 13,000 rpm). The nanoparticles are then resuspended in 6 mL of the ammonium acetate solution described above using an ultrasonic probe (1 minute) or by intensive stirring. After 30 seconds, 5 mL of a clindamycin phosphate solution (CLP, disodium salt; 3.8 mg, 7.0 µmol) are added over 10 seconds and stirred for a further 10 minutes. In this way, [ZrO]²⁺< [CLP]²⁻< is deposited as an inorganic-organic hybrid compound as a shell on the BDQ core, forming BDQ@[ZrO]²⁺< [CLP]²⁻< core@shell nanocontainers. The resulting suspension is centrifuged (10 min, 25000 rpm) and the BDQ@[ZrO]²⁺< [CLP]²⁻< core@shell nanocontainers are resuspended in deionized water.

[0077] The BDQ@[ZrO] 2+< [CLP] 2-< core@shell nanocontainers containing two antibiotic agents are very stable as a colloidal suspension in water. Electron microscopy reveals a mean diameter of approximately 40 nm, with the core having a mean diameter of approximately 20 nm and the shell having a thickness of approximately 10 nm.

[0078] The nanocontainer core and / or nanocontainer shell can be fluorescently labeled by adding 3,3'-diethylthiadicarbocyaniniodide to the BDQ solution (1 mol% based on the amount of BDQ) and / or adding Dynomics-647-uridine triphosphate to the CLP solution (0.1 mol% based on the amount of CLP). The absorption and emission behavior of the respective fluorescent dyes is known to those skilled in the art. Example 1.8: Production of ITC@[ZrO] 2+< [FLU] 2-< -nanocontainers:

[0079] Tocopherol phosphate (disodium salt; 3.8 mg, 7.0 µmol) and ammonium acetate (36.1 mg; 468 µmol) are each dissolved in 6 mL of deionized water. Both solutions are combined and cooled in an ice bath. A solution of irinotecan (ITC; 4.2 mg, 7.2 µmol) in 0.2 mL of benzyl alcohol is injected with vigorous stirring. During and after injection, the solution / suspension is further mixed using a 10-second ultrasonic pulse. The resulting suspension containing ITC nanoparticles, which will form the nanocontainer core, remains colloidally stable for approximately 1 hour.

[0080] In the next step, the suspension of ITC nanoparticles is added dropwise over 2 minutes to 9 mL of a ZrOCl₂ solution (octahydrate; 6.8 mg, 37.9 µmol) with intensive stirring. This suspension is stirred for a further 10 minutes. The mixture is then centrifuged (10 minutes, 13,000 rpm). The nanoparticles are then resuspended in 6 mL of the ammonium acetate solution described above using an ultrasonic probe (1 minute) or by intensive stirring. After 30 seconds, 5 mL of a fludarabine solution (FLU, disodium salt; 2.9 mg, 7.0 µmol) are added over a period of 10 seconds and stirred for a further 10 minutes. In this way, [ZrO]²⁺< [FLU]²⁻< is deposited as an inorganic-organic hybrid compound as a shell on the ITC core, so that ITC@[ZrO]²⁺< [FLU]²⁻< core@shell nanocontainers are formed. The resulting suspension is centrifuged (10 min, 25000 rpm) and the ITC@[ZrO]²⁺< [FLU]²⁻< core@shell nanocontainers are resuspended in deionized water.

[0081] The ITC@[ZrO] 2+< [FLU] 2-< core@shell nanocontainers containing two chemotherapeutic agents are very stable as a colloidal suspension in water. Electron microscopy reveals a mean diameter of approximately 60 nm, with the core having a mean diameter of approximately 30 nm and the shell having a thickness of approximately 15 nm.

[0082] By adding Lumigen Red to the ITC solution (1 mol% based on the amount of ITC) and / or adding Dynomics-546-uridine triphosphate to the FLU solution (0.1 mol% based on the amount of FLU), the nanocontainer core and / or nanocontainer shell can be fluorescently labeled. The absorption and emission behavior of the respective fluorescent dyes is known to those skilled in the art. Example 1.9: Production of PAC@[GdO] +< [SN-38] -< -nanocontainers:

[0083] Tocopherol phosphate (disodium salt, 3.8 mg, 7.0 µmol) and ammonium acetate (36.1 mg, 468 µmol) are each dissolved in 6 mL of deionized water. Both solutions are combined and cooled in an ice bath. A solution of paclitaxel (PAC; 6.1 mg, 7.2 µmol) in 0.2 mL of DMSO is injected with vigorous stirring. During and after injection, the solution / suspension is further mixed using a 10-second ultrasonic pulse. The resulting suspension containing PAC nanoparticles, which will form the particle core, remains colloidally stable for approximately 1 hour.

[0084] In the next step, the suspension of PAC nanoparticles is added dropwise over 2 minutes to 9 mL of a GdCl₃ solution (hexahydrate, 14.1 mg, 37.9 µmol) with intensive stirring. This suspension is stirred for a further 10 minutes. The mixture is then centrifuged (10 minutes, 13,000 rpm). The nanoparticles are then resuspended in 6 mL of deionized water using an ultrasonic probe (1 minute) or by intensive stirring. After 30 seconds, 5 mL of an alkaline SN-38 solution (SN-38 as the active metabolite of irinotecan, pH 9, 2.7 mg, 7.0 µmol) are added over a period of 10 seconds and stirred for a further 10 minutes. In this way, [GdO]< [SN-38]< is deposited as an inorganic-organic hybrid compound as a shell on the PAC core, forming PAC@[GdO]< [SN-38]< - core@ shell nanoparticles. The resulting suspension is centrifuged (25,000 rpm, 10 min), and the PAC@[GdO]< [SN-38]< - core@ shell nanoparticles are resuspended in deionized water.

[0085] The PAC@[GdO] +< [SN-38] -< -core@shell nanoparticles containing two chemotherapeutic agents are very stable as a colloidal suspension in water. Electron microscopy reveals a mean diameter of approximately 50 nm, with the core having a mean diameter of approximately 20 nm and the shell having a thickness of approximately 15 nm.

[0086] By adding Lumigen Green to the PAC solution (1 mol% based on the amount of PAC) and / or adding Dynomics-647-uridine triphosphate to the SN-38 solution (0.1 mol% based on the amount of SN-38), the particle core and / or particle shell can be fluorescently labeled. The absorption and emission behavior of the respective fluorescent dyes is known to those skilled in the art. Example 2: Recording the core@shell nanocontainers

[0087] Exemplary 2 concerns the evaluation of the uptake of core@shell nanocontainers by pancreatic tumor cells. Here, ITC@[ZrO] 2+< [FLU] 2-< core@shell nanocontainers were compared with corresponding reference nanocontainers that do not contain a pharmaceutically active substance.

[0088] Figure 3A The image shows a highly magnified uptake / internalization of particles after 48 h incubation of the core@shell nanocontainers with the tumor cells (PancO2 cell line). As expected, the ITC@[ZrO] 2+< [FLU] 2-< core@shell nanocontainers resulted in high toxicity, leaving only a few cells in the preparation. This is shown in the Figure 3B (Overview shot, 10x magnification) even more clearly visible. Example 3: Effectiveness of the core@shell nanocontainers

[0089] Example 3 demonstrates the efficacy of the core@shell nanocontainers on murine breast cancer cells. Measurements were performed using a CellTiter 96® < AQueous One Solution Cell Proliferation Assay (MTS), a colorimetric method for determining cell viability.

[0090] As the Fig. 4 The treatment of tumor cells with ITC@[ZrO] 2+< [FLU] 2-< -core@shell nanocontainer leads to concentration-dependent toxicity, while incubation with the reference nanocontainers, which do not contain any pharmaceutically active agent, shows no negative effect on cell growth.

Claims

1. A nanocontainer, comprising a lipophilic core, wherein the lipophilic core comprises at least one lipophilic compound selected from a lipophilic, pharmaceutically active ingredient or a lipophilic detection reagent; and a hydrophilic shell enclosing the lipophilic core, wherein the hydrophilic shell is composed of an inorganic-organic hybrid compound as an ionic compound, wherein the inorganic-organic hybrid compound is composed of an inorganic metal cation selected from Mn2+, Sc3+, Y3+, La3+, Fe2+, Fe3+, [ZrO]2+, [HfO]2+, Bi3+, Gd3+ or a lanthanide Ln2+ or Ln3+ or a hydrated form of these cations, and an organic active ingredient anion or a hydrophilic detection reagent anion, each of which contains at least one phosphate, phosphonate, sulfate, sulfonate, carbonate or carboxylate group as a functional group, wherein the hydrophilic active ingredient anion or the hydrophilic detection reagent anion in the inorganic-organic hybrid compound is selected from the group of antibiotics consisting of clindamycin phosphate, erythromycin phosphate, tedizolid phosphate, CpG oligodeoxynucleotides, fosfomycin, moxalactam, ceftriaxone, amoxicillin, phenoxymethylpenicillin, aztreonam, moxifloxacin, and bacitracin; or the group of antiviral drugs consisting of idoxuridin phosphate, acyclovir phosphat, penciclovir phosphate, ganciclovir phosphate, remdesivir phosphat, galidesivir phosphat, vidarabin phosphate, ribavirin phosphate, abacavir phosphate, stavudine phosphate, adefovir, fosamprenavir, fostemsavir, tenofovir, brincidofovir, cidofovir, foscarnet, ivermectin, bevirimat, and zanamivir, or the group of chemotherapeutic drugs consisting of 5-fluoro-2'-deoxyuridine-5'-monophosphate, gemcitabine monophosphate, gemcitabine triphosphate, fludarabine, pemetrexed, methotrexate, estramustine phosphate, streptozotocin phosphate, mitoxantrone phosphate, azacitidine phosphate, cyclophosphamide mustard, SN-38, melphalan, chlorambucil, and bendamustine; or the group of anti-inflammatory drugs consisting of betamethasone phosphate, dexamethasone phosphate, prednisolone phosphate, sulfasalazine, acetyl salicylate, methotrexate, ibuprofen, naproxen, and ketoprofen; or the group of fluorescent dyes consisting of phenylumbelliferone phosphate, flavin mononucleotide, methylfluorescein phosphate, resorufin phosphate, Dynomics-546-uridine triphosphate, Dynomics-647-uridine triphosphate, Amaranth Red, Chicago Sky Blue, Direct Blue 71, Congo Red, Nuclear Fast Red, Acid Red 97, and Evans Blue, wherein a pharmaceutically active ingredient is a substance used as an agent for curing or preventing human or animal diseases, as well as a substance intended to be used in or on the human or animal body to restore, improve or influence human or animal body functions, and a detection reagent is a substance that can be detected / localized in the body after administration, for example optically via fluorescence in the case of a fluorescent dye or also through X-ray absorption, magnetic measurements or based on their radioactive radiation.

2. The nanocontainer according to claim 1, wherein the at least one lipophilic, pharmaceutically active ingredient or lipophilic detection reagent is selected from the group of antibiotics consisting of delamanid, bedaquiline, benzothiazinones such as benzothiazinon 043, clofazimine, rifampicin, levofloxacin, cefaclor, cefpodoxime, imipenem, meropenem, ciprofloxacin, levofloxacin, norfloxacin, chloramphenicol, trimethoprim, azithromycin, metronidazole, linezolid, tyrothricin, rifabutin, rifaximin, fusidic acid, doxycycline, hydroxytamoxifen, and pantoprazole; or the group of antiviral drugs consisting of amantadine, rimantadine, penciclovir, emivirine, FGI-106, maraviroc, sofosbuvir, baloxavirmarboxil, etravirine, nevirapine, atazanavir, indinavir, lopinavir, nelfinavir, tipranavir, boceprevir, telaprevir, dolutegravir, raltegravir, and tecovirimat; or the group of chemotherapeutic drugs consisting of ifosfamide, paclitaxel, docetaxel, abraxan, taxoter, mechlorethamine, erlotinib, gefitinib, imatinib, vemurafenib, cisplatin, daunorubicin, epirubicin, lomustine, vismodegib, actinomycin D, vinorelbine, camptothecin, topotecan, irinotecan, etoposide, teniposide, and mercaptopurine; or the group of anti-inflammatory drugs consisting of cannabidiol, triamcinolone, budesonide, diclofenac, cortisol, calcitriol, leflunomide, and non-steroidal anti-inflammatory drugs; or the group of fluorescent dyes consisting of Lumogen Red, Lumogen Orange, Lumogen Yellow or Lumogen Green, magnesium phthalocyanine, zinc phthalocyanine, 1,1'-diethyl-4,4'-carbocyanine iodide, 3,3'-diethylthiadicarbocyanine iodide, magnesium tetraphenylporphyrin, and phthalocyanine.

3. The nanocontainer according to claim 1 or 2, wherein the mass of the lipophilic, pharmaceutically active ingredient and / or the lipophilic detection reagent is 50 to 100% by weight, based on the total mass of the lipophilic core.

4. The nanocontainer according to one of claims 1 to 3, wherein the lipophilic core further comprises a lipophilic excipient.

5. The nanocontainer according to one of claims 1 to 4, wherein the lipophilic core has a diameter of 10 to 150 nm, measured by electron microscopy.

6. The nanocontainer according to one of claims 1 to 5, wherein the mass of the hydrophilic, pharmaceutically active ingredient and / or the detection reagent is 50 to 90% by weight, based on the total mass of organic anions in the shell,7. The nanocontainer according to one of claims 1 to 6, wherein the nanocontainer has a diameter of 20 to 300 nm, measured by electron microscopy.

8. The nanocontainer according to one of claims 1 to 7, wherein the at least one lipophilic compound is a lipophilic, pharmaceutically active ingredient.

9. The nanocontainer according to one of claims 1 to 8, wherein the inorganic-organic hybrid compound is composed of an inorganic metal cation as defined above and an organic active ingredient anion to form the hydrophilic shell.

10. A method for producing a nanocontainer according to one of claims 1 to 9 by means of solvent-antisolvent method, comprising the steps of (I) providing a solution of the at least one lipophilic compound, wherein the at least one lipophilic compound is a lipophilic, pharmaceutically active ingredient and / or a lipophilic detection reagent; (II) injecting the solution provided in step (I) into a polar solvent; and (III) adding the organic anion and the inorganic cation which form the inorganic-organic hybrid compound to form the hydrophilic shell.

11. A nanoparticle, comprising: the nanocontainer according to one of claims 1 to 9, functionalized with at least one element selected from the group consisting of antibodies, peptides, 5-aminolevulinic acid, folic acid derivatives, albumin derivatives, saccharides and ligands, for specific binding to receptors of cells.

12. A nanocontainer according to one of claims 1 to 9 and / or a nanoparticle according to claim 11 for use in the treatment of infections caused by bacteria and / or viruses, inflammatory autoimmune reactions or for the treatment of tumors.