105 results about "Brain targeting" patented technology

The invention discloses brain-targeted stem cell membrane bionic cationic liposome as well as a preparation method and application thereof. The preparation method comprises the following steps: extracting and purifying to obtain a stem cell membrane; preparing a cationic liposome; the stem cell membrane and the cationic liposome are fused to obtain the stem cell membrane bionic cationic liposome, and the relative dosage of the stem cell membrane and the cationic liposome is that the mass ratio of the total protein mass of the stem cell membrane to the total fat mass of the cationic liposome is 1: (2-24). The stem cell membrane bionic cationic liposome constructed by using the purified stem cell membrane has high brain targeting ability, low immune irritation and efficient nucleic acid drug carrying ability, can break through the blood brain barrier, realizes efficient targeting delivery of nucleic acid drugs to cells of the brain including neurons, and has good application prospects. Particularly, the polypeptide can be used as a targeted delivery platform of nucleic acid drugs for targeted therapy of cerebral diseases, especially cerebral arterial thrombosis.

The invention discloses a non-natural amino acid as well as a preparation method and application thereof. The novel non-natural amino acid is obtained by introducing long and soft side chain amino acid into a classical ASF side chain for the first time, the stability of the obtained non-natural amino acid is enhanced, the reaction radius of the non-natural amino acid is increased, the non-natural amino acid can touch amino acid residues with farther distance, and the reactivity is improved. In addition, compared with other covalent amino acids, the covalent amino acids have higher reaction rate and binding efficiency. The polypeptide and related drugs obtained based on the non-natural amino acid can be high in safety, can cross a blood brain barrier to realize brain targeting, and have better anti-tumor activity, so that the polypeptide and related drugs have extremely high medical value.

The invention provides a ziconotide nasal-brain delivery preparation which is high in brain targeting, safe and noninvasive and directly enters the brain through nasal administration. The nasal-brain delivery preparation comprises an active component ziconotide and an absorption enhancer, wherein the absorption enhancer is selected from one or more of dodecyl-beta-D-maltoside (DDM), menthol, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), sodium glycocholate (SGC) and related derivatives thereof. The absorption enhancer with a specific type and content and the ziconotide cooperate and act together, so that the ziconotide bypasses a blood brain barrier, enters the brain through a nasal olfactory mucous membrane, forms a medicine storage bank in an olfactory bulb, is slowly released to the brain and keeps a long-term medicine effect, and therefore, a traditional ziconotide intrathecal administration mode is abandoned; the ziconotide nasal-brain administration mode is created, and the ziconotide nasal-brain administration method is a new-generation therapy for pain diseases related to the central nervous system.

The invention discloses a curcumin-loaded brain-targeted drug delivery system as well as a preparation method and application thereof. The delivery system comprises a carrier macrophage and a curcumin drug, the curcumin nano-drug is prepared by encapsulating curcumin with a lipoic acid modified cyclodextrin conjugate, then macrophages and the curcumin nano-drug are mixed, and co-incubation is carried out, so that the curcumin nano-drug is constructed. The brain-targeted macrophage drug delivery system loaded with curcumin is a multifunctional composite drug with brain targeting property for treatment of cerebral arterial thrombosis. A brain-targeted macrophage drug delivery system loaded with the curcumin nano-drug gathers in cerebral apoplexy tissues, phenotypic transformation of inflammatory microglial cells is promoted, and a pro-inflammatory microenvironment is improved; the oxidative stress pressure of the stroke part is improved; the two effects promote each other, the stroke microenvironment is improved, the functions of neuronal cells are saved, the synergistic nerve protection effect can be achieved in the aspect of treating ischemic cerebral apoplexy, and potential safety hazards are reduced.

The present invention provides a high brain targeting, safe and noninvasive nasal-brain delivery preparation, which is characterized in that the nasal-brain delivery preparation comprises nimodipine, a good solvent, a diluent and an absorption enhancer, the good solvent is diethylene glycol monoethyl ether, and the absorption enhancer is phospholipid. The nasal-brain delivery preparation is prepared from a good solvent, a diluent, an absorption enhancer and the like according to a specific proportion. Nimodipine serving as an active ingredient is enriched in cerebrospinal fluid and brain tissues through a specific upper nasal meatus administration technology, so that the treatment effect of nimodipine is achieved; and meanwhile, the blood entering proportion is reduced, so that the cardiovascular toxicity and hepatotoxicity are reduced. In addition, the preparation formula has no irritation to local parts of the nasal cavity, and the compliance of a patient is improved.

The invention discloses design and synthesis of a series of brain-targeted ginsenoside Rg1 derivatives and application of the brain-targeted ginsenoside Rg1 derivatives in treatment of Alzheimer's disease. According to the invention, ginsenoside Rg1 and polyethylene glycol with a specific chain length are covalently linked to successfully construct the derivative capable of enhancing the penetrating power of the blood-brain barrier. The series of derivatives provided by the invention not only solve the problems of poor brain targeting and insufficient stability of natural Rg1, but also can inhibit neuroinflammation by regulating and controlling an NLRP3 / caspase-1 signal channel in an LPS-induced neuroinflammation model, and finally, the learning and memory ability is remarkably improved. The product is simple and convenient in preparation process and good in biological safety, and a new candidate compound is provided for developing a new generation of Alzheimer disease treatment medicines.

The present invention discloses a fusion protein, a high-density lipoprotein containing the fusion protein, and a bionic nano-drug, as well as preparation and application thereof. The fusion protein comprises an alpha-helical amphipathic polypeptide and a neuron targeting peptide. The high-density lipoprotein containing the fusion protein is used as a bionic nano-carrier to achieve brain-targeted delivery of the drug through intravenous administration, which saves manpower, material resources and financial resources compared with in situ administration to the brain, and significantly improves patient compliance.

The invention provides a nomeline nasal-brain delivery preparation for transnasal region mucosa administration, and an auxiliary material mixture of the nasal-brain delivery preparation comprises 1) phospholipid, and 2) any one of diluent ethyl oleate, isopropyl myristate, sesame oil or castor oil; optionally, the auxiliary material mixture can also comprise 3) a dissolving agent such as ethanol or diethylene glycol monoethyl ether, the auxiliary material mixture is a non-aqueous system, and a solution prepared from the mixture of the two or three auxiliary materials can be absorbed by the nasal meatus olfactory mucosa after being administrated through the nasal region mucosa, can be quickly conducted to the brain olfactory bulb region along olfactory nerves and cerebrospinal fluid, and can be used for treating the brain olfactory bulb. The problems that the peripheral side effect is high due to poor brain targeting of the medicine, the medicine takes effect slowly and the like are solved.

The invention relates to a bionic nano CO generator as well as preparation and application thereof, belongs to the technical field of medicines, and solves the problem that a CO delivery system which can synergistically promote neuroprotection and neurogenesis and has brain targeting and controlled release capabilities is urgently required to be developed at present. According to the technical scheme, the bionic nano CO generator comprises a drug-loaded particle inner core and a covering film, the drug-loaded particle inner core comprises hollow mesoporous CeO2 nano particles and MnCO loaded on the hollow mesoporous CeO2 nano particles, and the covering film is a macrophage membrane and wraps the drug-loaded particle inner core. The compound is used for apoplexy treatment administration by integrating neuroprotection and enhancing innovative dual channels of endogenous nerve growth, and is expected to significantly reduce brain injury after cerebral apoplexy and restore neurological functions so as to relieve the worry about high death rate and long-term disability after cerebral ischemia-reperfusion injury.

Disclosed in the present invention are a preparation method for a brain-targeting agomelatine nasal spray micelle and use thereof, which belong to the technical field of pharmaceutical formulations. According to the present invention, an injectable pharmaceutical excipient polyethylene glycol (15)-hydroxystearate (HS15) is taken as a carrier material, HS15 and agomelatine are dissolved in an organic solvent, and the resulting solution is subjected to rotary evaporation under reduced pressure to form a uniform film, which, upon hydration, forms an agomelatine micelle solution capable of being sprayed nasally for treating depression and insomnia. According to the present invention, the problem of low oral bioavailability of agomelatine due to poor solubility, serious first pass effect of hepar, difficulty in penetrating a blood-brain barrier, etc., is solved. The micelle structure constructed in the present invention is quickly delivered into the brain after nasal administration, and it is stable in cerebrospinal fluid and can achieve slow release of the drug, thereby improving the intracerebral bioavailability of the drug and achieving high brain targeting property and low systemic toxic and side effects. The micelle structure has good clinical application value and market prospects.

Methods for treating Alzheimer's disease and other neurodegenerative disorders in which the capacity of microglia and / or astrocytes has been altered and impaired are described. The method comprises the step of carrying out brain targeting on PD-L1 by using a brain targeting nanogel which is loaded with a PDL1 antibody and is functionalized by two specific targeting ligands. The nanogel can successfully cross the blood brain barrier to release the antibody, reduce the expression of PD-L1 in the brain, and maintain the integrity of BBB at the same time.

The invention provides a POCD treatment medicine composition with dendrobine delivered by a nano-carrier and application, and belongs to the technical field of medicine. The composition consists of dendrobine, a nano-carrier material and a stabilizer, wherein a nano-carrier is PLGA (poly (lactic-co-glycolic acid)) nanoparticles or lipidosome. The particle size of the composition is 50-150nm, the polydispersity index is less than 0.3, and the loading capacity of dendrobine is 5-15%. The invention also provides two preparation methods of the composition. The PLGA nanoparticles are prepared by adopting an emulsification-solvent evaporation method; the liposome is prepared by adopting a film hydration-ultrasonic extrusion method, and each process parameter is specifically limited. The pharmaceutical composition can significantly improve the brain targeting and bioavailability of dendrobine, and can be used for preparing drugs for preventing or treating postoperative cognitive impairment (POCD), and the administration route can be intravenous injection or nasal administration.

The invention relates to an anti-epileptic polypeptide coupling medicine and a preparation method and application thereof, the polypeptide coupling medicine comprises an Fmoc protecting group, a permeation accelerating peptide and a cell penetrating peptide which are sequentially connected from the N end to the C end, and the permeation accelerating peptide is connected with an anti-epileptic medicine molecule. According to the invention, by fully utilizing the treatment requirements of epileptic seizure and the technical advantages of intranasal drug delivery, through the collaborative design of the protecting group, the functional polypeptide sequence and the anti-epileptic drug, the defects of poor brain targeting property, easy cyclization of a polypeptide carrier, low intranasal delivery efficiency and the like of the traditional anti-epileptic drug are overcome, non-invasive, efficient and low-toxicity epilepsy treatment is realized, and the application prospect is wide. And the preparation process is simplified, the clinical transformation requirement is met, and meanwhile, a new strategy is provided for non-invasive brain delivery of neuropeptide drugs.

The invention discloses preparation of supramolecular nanoparticles self-assembled by polypeptide coupling drugs with stimulation responsiveness and application of the supramolecular nanoparticles in brain tumors. The supramolecular nanoparticles comprise a requinomod analogue and a camptothecin analogue. A requinomod analogue and a camptothecin analogue are connected to a brain targeting peptide through a sensitive peptide, and are further self-assembled to form supramolecular nanoparticles, so that the brain targeting ability and intracerebral retention efficiency of the drug are improved. The polypeptide coupled drug supramolecular nanoparticles provided by the invention show excellent capabilities of killing tumor cells and polarizing anti-inflammatory macrophages in vivo and in vitro, have a strong inhibition effect on brain tumors, and have huge clinical application value.

The invention discloses a borneol modified erythrocyte membrane coated dendritic macromolecule bionic nano drug delivery system and preparation and application thereof, the bionic nano drug delivery system comprises an erythrocyte membrane and a drug loaded dendritic macromolecule coated in the erythrocyte membrane, the surface of the erythrocyte membrane is modified with targeted molecule borneol, the drug is an anti-tumor drug, such as bufotalin. In combination with a nasal drop administration mode, not only can the brain targeting efficiency of the glioma treatment drug be improved, but also the glioma treatment drug has immune escape and tumor microenvironment response capabilities, the in-vivo circulation time of the drug is effectively prolonged, and the glioma treatment effect is further improved. The design that the dendritic macromolecules are coated with the modified erythrocyte membranes combines the biocompatibility of natural cell membranes and the multifunctionality of nanoparticles, and the dendritic macromolecules have huge application potential in the fields of drug delivery, immune regulation, detoxification, targeted therapy and the like.

The invention belongs to the technical field of biological medicine, and discloses a brain-targeted nano drug delivery system, a preparation method and application. According to the invention, dipentaerythritol-polycaprolactone-histidine (DPE-PCL-HIS) is used as a basic drug carrier, and drug curcumin (Cur) molecules are entrapped in a physical embedding manner; and modifying bovine serum albumin (BSA) grafted with a bifunctional intermediate connection compound 4-(N-maleimide methyl) cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt (Sulfo-SMCC) on a precoating layer, and finally connecting an apolipoprotein E mimic peptide as a brain-targeting ligand, so as to construct the brain-targeting bionic protein crown nano drug delivery system, wherein the bovine serum albumin (BSA) is grafted with the bifunctional intermediate connection compound 4-(N-maleimide methyl) cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt (Sulfo-SMCC). According to the prepared brain-targeted nano drug delivery system, apolipoprotein E mimic peptide [RLLRKRLK (PEG2000) RLGWC] is used as a ligand and enters the brain under the transendocytosis action of the apolipoprotein E mimic peptide [RLLRKRLK (PEG2000) RLGWC] and a blood-brain barrier (BBB) surface receptor, the blood-brain barrier permeability of a drug is increased, the brain targeting property and bioavailability of drug-loaded nanoparticles are improved, and the brain-targeted nano drug delivery system has wide application prospects in the aspect of treating brain diseases.

The invention provides a biotinylated Angiopep-2 modified targeting nano material as well as a preparation method and application of the biotinylated Angiopep-2 modified targeting nano material. According to the preparation method of the biotinylated Angiopep-2 modified targeting nano-material, Angiopep-2 is directionally anchored through a high-affinity biotin-streptavidin system, ligand conformation inactivation caused by chemical coupling is avoided, targeting activity is maintained, the used Angiopep-2 can help nanoparticles to be specifically recognized and combined and mediate the nanoparticles to cross a blood brain barrier to enter the brain, and the targeting nano-material can be used for preparing the targeted nano-material. The drug concentration in brain tissues is increased, so that the cure rate of brain diseases is improved, the brain targeting efficiency is far higher than that of transferrin and lactoferrin, and the application value is great; by entrapping curcumin and quercetin, a hydrophilic shell is provided, so that the water solubility of curcumin and quercetin is improved, and the bioavailability of curcumin and quercetin is improved.

The invention provides a hemicyanine photosensitizer as well as a preparation method and application thereof, and belongs to the field of biological medicines. A hemicyanine dye-based molecule with a D-pi-A structure is developed through donor substitution engineering, and the structure of the hemicyanine dye-based molecule is shown as a formula I in the specification. The hemicyanine dye-based molecule has excellent spectral performance. The PLH1100 nano assembly further constructed on the basis of the hemicyanine dye-based molecule has excellent brain targeting property, tumor enrichment property, light stability and biocompatibility as well as excellent photothermal conversion efficiency and NIR-II tumor imaging capability, and is suitable for photothermal immunotherapy of glioblastoma. In addition, the invention also finds that the PLH1100 can significantly enhance the curative effect of a bispecific T cell adapter (Fn14 * CD3BiTE) aiming at an Fn14 target spot, the combination of the PLH1100 and the Fn14 * CD3BiTE adapter plays a synergistic role in photothermal immunotherapy, a new way is opened up for clinical treatment of glioblastoma, and the PLH1100 and the Fn14 * CD3BiTE have significant clinical application potential. # imgabs0 #

The invention discloses a polypeptide-modified black phosphorus nanosheet composite material for brain targeting and a preparation method thereof, the invention provides the polypeptide-modified black phosphorus nanosheet composite material for brain targeting and the preparation method thereof, and the black phosphorus nanosheet composite material has good drug loading capacity and excellent photo-thermal capacity, and can be applied to brain targeting. The problem of solubility of the resveratrol is solved, and the bioavailability of the resveratrol is improved. The black phosphorus nanosheet composite material disclosed by the invention is modified by ANG polypeptide, penetrates through a blood brain barrier through LRP-1 receptor mediated endocytosis and enters the brain, and has an obvious brain targeting characteristic. Meanwhile, under near-infrared illumination, the blood-brain barrier permeability of the black phosphorus nanosheet composite material can be further improved. The black phosphorus nanosheet composite material disclosed by the invention has a remarkable treatment effect on ischemic brain injury under the conditions of polypeptide modification and near-infrared illumination.

The invention discloses a brain-targeted nasal-spray amphotericin B phospholipid complex and a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations, the brain-targeted nasal-spray amphotericin B phospholipid complex is prepared by adopting a film dispersion method, and the preparation method comprises the following steps: dissolving 15-hydroxystearic acid polyethylene glycol ester, phospholipid, cholesterol, amphotericin B and optional other auxiliary components in a solvent, removing the solvent until a film is formed, and drying to obtain the brain-targeted nasal-spray amphotericin B phospholipid complex. And carrying out hydration dispersion to obtain the amphotericin B-loaded phospholipid complex. According to the amphotericin B sodium deoxycholate injection, the problems that the traditional amphotericin B sodium deoxycholate injection is high in renal toxicity, the intrathecal injection is poor in solubility, and low in bioavailability and patient compliance, large in side effect and the like due to the fact that the traditional amphotericin B sodium deoxycholate injection is difficult to penetrate through a blood brain After nasal administration, the drug is quickly delivered into the brain, so that the slow release of the drug is realized, the intracerebral bioavailability of the drug is improved, high brain targeting and low systemic toxic and side effects are realized, and good clinical application value and market prospect are achieved.

The application discloses a preparation method of a novel hierarchical drug release lemon exosome nano preparation and application thereof in brain glioma treatment and belongs to the field of nano medicines. The method comprises the following steps: extracting and purifying lemon exosomes, introducing an anti-glioma drug and a first part of LRP1 up-regulating agent into the inner cavity of the exosomes through electroporation, instantaneously constructing a tumor microenvironment responsive nanogel core to fix the drug, embedding a second part of LRP1 up-regulating agent into the lipid layer of the exosome, modifying Angiopep-2 to realize brain targeting, and obtaining the nano preparation through purification. The preparation has the hierarchical drug release characteristics of outer layer early release and inner cavity delayed release, can improve the efficiency of drug crossing the blood-brain barrier and accumulation at the tumor site, enhance the anti-glioma effect, solves the technical problem that the existing drug loading system is difficult to realize multi-drug phased release, and provides a new strategy for brain glioma treatment.

The invention discloses a temozolomide spherocrystal based on nano confinement crystallization regulation and a method and application thereof. The preparation method of the temozolomide spherocrystal based on nano confinement crystallization regulation and control comprises the following steps: dissolving glycyrrhizic acid and temozolomide in pure water under an ultrasonic condition, adjusting the pH value to 3-4, heating until the solution is clear, and cooling to 0-5 DEG C under a stirring condition to obtain the temozolomide spherocrystal based on nano confinement crystallization regulation and control. Compared with the temozolomide raw material I crystal form, the temozolomide spherocrystal disclosed by the invention shows excellent nasal administration characteristics, including uniform particle size, high sphericity and excellent fluidity. Cell experiments show high cytotoxicity (IC50 = 51.9 [mu] g mL <-1 >) to glioblastoma, and in vivo experiments prove efficient brain targeting ability of the polypeptide. The preparation method has the characteristics of mild preparation conditions, easiness in process control, good reproducibility, high brain targeting property and the like, and is suitable for treating cancers delivered into the brain through the nose.

The invention belongs to the technical field of biological medicine, and discloses a brain targeting peptide-nervonic acid conjugate crossing a blood brain barrier and a preparation method and application thereof.The brain targeting peptide and nervonic acid are covalently coupled, so that the targeting property of nervonic acid is improved, the blood brain barrier crossing capacity of nervonic acid is enhanced, and by increasing the accumulation amount of nervonic acid in brain parenchyma, the brain targeting peptide-nervonic acid conjugate crossing the blood brain barrier is obtained. Precise delivery of nervonic acid is achieved, and the brain-targeted peptide-nervonic acid conjugate can be applied to treatment of brain-related diseases.

The invention discloses a traditional Chinese medicine monomer nanoparticle oral delivery system based on intestinal liver circulation and a preparation method thereof, spherical nanoparticles (SA NPs) with the particle size of 194 + / -20 nm are formed through self-assembly of threat resin acid (SA), and the limitation of a traditional nano carrier is broken through: the oral bioavailability reaches 34.7% by utilizing an ASBT-mediated intestinal liver circulation mechanism; the gastric acid environment is tolerated (the pH is stable at 1.5), and after penetrating through the intestinal epithelium, the drug is targeted to ischemic brain tissues; the medicine has carrier-medicine dual functions, and the cerebral infarction volume is reduced by 34.1% when the medicine is singly used; after the neuroprotective peptide NA1 is loaded (the drug loading capacity is 5.8 wt%), the infarct volume is reduced by 68.7% through synergism. The system is suitable for pre-hospital first aid of cerebral apoplexy, and the freeze-dried powder can be stored at normal temperature for 12 months. The delivery system has a great application prospect in preparation of drugs for treating acute ischemic stroke needing rapid brain targeting.

The invention belongs to the technical field of biological medicine, and particularly relates to a nano-micelle preparation loaded with minocycline and application of the nano-micelle preparation to treatment of cerebral hemorrhage, the nano-micelle preparation is prepared by taking a polyethylene glycol-polycaprolactone nano material PEG3000-PCL2000 as a carrier, and jointly loading minocycline MINO and a CD147 monoclonal antibody Anti-CD147, so that the nano-micelle preparation is prepared. And the bionic nano-drug MINO (at) PNM (at) CD147 with an active targeting function is constructed. The nano-micelle preparation has a brain targeting property and can be enriched in cerebral hemorrhage tissues, so that the local drug concentration and the treatment efficiency are remarkably improved; the traditional Chinese medicine composition can improve neurological impairment caused by cerebral hemorrhage and significantly reduce the volume of cerebral hematoma, and has an obvious treatment effect on cerebral hemorrhage; the number of inflammatory cells in the peripheral area of hematoma and expression of inflammatory mediators can be remarkably reduced, and therefore the inflammatory response in cerebral hemorrhage tissue is relieved.

The application discloses application of RVG-Exo-miR-3059-5 in treating cerebral stroke. The RVG-Exo-miR-3059-5 is prepared by using gene engineering technology to perform brain targeting modification on EPCs-Exo and load miR-3059-5p drugs. The experiment proves that the RVG-Exo-miR-3059-5 can effectively target brain tissues, can prevent or treat cerebral stroke, and can improve the prognosis of cerebral stroke patients.

The invention discloses a proteolysis targeting chimeric molecule capable of degrading PTBP1 in a targeting manner as well as a preparation method and application of the proteolysis targeting chimeric molecule. The invention relates to a protease targeted chimeric RNA-PTAC of a nucleic acid ligand. The protease targeted chimeric RNA-PTAC is formed by connecting an E3 ubiquitin ligase ligand pomalidomide and an RNA fragment capable of being specifically combined with PTBP1 protein through polyethylene glycol Linker. The invention relates to an RNA-PROTAC (Ribonucleic Acid-PROTAC) brain targeting delivery preparation, which is a complex obtained by coupling cell penetrating peptides TAT and RVG (Recombinant Virus Growth) with the RNA-PROTAC. According to the TR + RNA-PROTAC complex disclosed by the invention, the targets of efficiently degrading PTBP1 protein in vitro and degrading PTBP1 protein in a brain in a targeted manner in vivo are achieved through the complex, and in-vivo experiments also prove that the TR + RNA-PROTAC complex can be used for treating learning and memory disorders of mice caused by A beta and shows a good curative effect of resisting Alzheimer's disease.

The invention belongs to the field of fluorescent probes, and discloses a selenium cyano fluorescent probe for high-selectivity recognition of H2S as well as a preparation method and application of the selenium cyano fluorescent probe. The probe adopts dicyanoisophorone as a fluorophore skeleton and-SeCN group as a novel recognition site, and the structural formula is shown in the specification. The dicyanoisophorone has relatively large Stokes shift during release, so that the interference of autofluorescence on signal detection is reduced, and the dicyanoisophorone is connected with a-SeCN group through a condensation reaction. On the basis of a double nucleophilic substitution strategy, H2S induces conversion of-SeCN into-Se-S, and near-infrared fluorophores are released through intramolecular self-cyclization. Researches show that the probe has high sensitivity, selectivity, good water solubility and thiol consumption resistance, the detection limit is as low as 20 nM, and the probe has good ratio signal and brain targeting ability.

The invention relates to an ultrasound-driven nerve regulation nano device for non-invasive treatment of epilepsy as well as a preparation method and application of the ultrasound-driven nerve regulation nano device. The ultrasound-driven nerve regulation nano device comprises a microenvironment response module, an ultrasound response module and a biological targeting module, the microenvironment response module is platinum nanoparticles, the ultrasonic response module is piezoelectric nanoparticles UIO-66-NH2, and the biological targeting module is brain targeting peptide; wherein the platinum nanoparticles are dispersed and embedded in a UIO-66-NH2 structure, and the brain-targeted peptide is modified on the surface of the UIO-66-NH2 structure. The nano device can effectively decompose hydrogen peroxide in an epilepsy focus area and reduce the oxidative stress level; the mechanical stress can be converted into an electric signal under the ultrasonic action to trigger neuron electrophysiological reaction, so that noninvasive precise regulation and control of an epilepsy reactive neural circuit are realized; meanwhile, the blood brain barrier can be efficiently traversed, and the cumulant of the epilepsy focus part in the brain is obviously enhanced through the synergistic effect of the external field ultrasound and the biological targeting module.

This invention relates to an insoluble drug formulation based on dialkylimidazolium biomimetic lipids, its preparation method, and its application, belonging to the field of pharmaceutical formulations. First, an insoluble drug is directly coupled to the primary amine group of the dialkylimidazolium biomimetic lipid or coupled via a linker to form a lipid-drug conjugate. Then, the lipid-drug conjugate, along with other lipid excipients, is dissolved in the dialkylimidazolium biomimetic lipid, and self-assembled in an aqueous phase to form a drug-loaded lipid nanoparticle delivery system with significant drug solubilizing effect. This drug delivery system exhibits good biocompatibility and plasma stability. It can cross the blood-brain barrier and selectively deliver drugs to glioma cells, achieving sustained release of the conjugated insoluble drug in the tumor microenvironment. This provides a new strategy for improving the pharmacokinetic properties of insoluble small-molecule antitumor drugs, including brain targeting, half-life, and bioavailability.