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CN-122005499-A - Bionic nano-particle applied to acute liver injury treatment and preparation method thereof

CN122005499ACN 122005499 ACN122005499 ACN 122005499ACN-122005499-A

Abstract

The invention relates to a bionic nano particle applied to acute liver injury treatment and a preparation method thereof, wherein a black phosphorus nano sheet is used as a carrier material, urolithin A is used as a therapeutic drug, a hybrid membrane prepared by mixing an erythrocyte membrane and an M2 macrophage membrane is used as a bionic shell, and drug loading is carried out through pH driving, so that the bionic nano particle is prepared. The nano particles can improve the solubility of urolithin A, enhance the application effect of the urolithin A in acute diseases, further enhance the antioxidation capability of the system in acute liver injury, and realize the double effects of prolonging the in vivo circulation time and enhancing the targeting of verification sites through an external hybrid membrane. The bionic nano-particles prepared by the method have good safety, the preparation method is easy to repeat, and the bionic nano-particles have good application prospect in the treatment of acute liver injury.

Inventors

  • ZHANG CHUANGNIAN
  • LAN Xiaoyun
  • YUE JINYU
  • CHEN ZHEN
  • YUAN XINXIN
  • LIU LIYUE
  • JIANG LIQIN

Assignees

  • 中国医学科学院生物医学工程研究所

Dates

Publication Date
20260512
Application Date
20260315

Claims (10)

  1. 1. The preparation method of the bionic nano-particles applied to acute liver injury treatment is characterized by comprising the following steps: step 1, preparing black phosphorus nano-sheets; step 2, loading the therapeutic drug on the black phosphorus nano-sheet to prepare a drug-loaded black phosphorus nano-sheet; And 3, coextruding a mixed solution of an erythrocyte membrane and an M2 type macrophage membrane to prepare a hybrid membrane, coating the hybrid membrane on the surface of the drug-loaded black phosphorus nano-sheet prepared in the step 2, and preparing the bionic nano-particles applied to acute liver injury treatment through coextruding.
  2. 2. The method for preparing the bionic nano-particles for treating acute liver injury according to claim 1, wherein the method comprises the following steps: The black phosphorus nano-sheet in the step 1 is a two-dimensional layered nano-sheet prepared from black phosphorus particles by a liquid-phase ultrasonic stripping method.
  3. 3. The method for preparing the bionic nano-particles for treating acute liver injury according to claim 1, wherein the method comprises the following steps: the operation of the step 1 is specifically as follows: Step 1.1, placing black phosphorus flakes in N-methyl pyrrolidone solution, performing ultrasonic treatment by using an ultrasonic crusher in an ice bath, and performing post-centrifugal treatment to obtain black phosphorus nano-flake precipitate; Step 1.2, quick freezing the pure ethanol solution by using liquid nitrogen, and extracting gas to obtain the pure ethanol solution without dissolved oxygen; And 1.3, re-dispersing the black phosphorus nano-sheet precipitate obtained in the step 1.1 by using ethanol without dissolved oxygen, centrifuging, and drying the obtained precipitate in vacuum heating to obtain the black phosphorus nano-sheet.
  4. 4. The method for preparing the bionic nano-particles for treating acute liver injury according to claim 1, wherein the method comprises the following steps: The therapeutic drug in the step 2 is urolithin A.
  5. 5. The method for preparing the bionic nano-particles for treating acute liver injury according to claim 1, wherein the method comprises the following steps: the operation of the step 2 is specifically as follows: mixing urolithin A ethanol solution with black phosphorus nanosheet ethanol suspension, fully performing ultrasonic dispersion, sequentially adjusting pH to be alkaline and neutral, loading urolithin A onto black phosphorus nanosheets, centrifuging, heating and drying the obtained precipitate in vacuum to obtain the medicine-carrying black phosphorus nanosheets.
  6. 6. The method for preparing the bionic nano-particles for treating acute liver injury according to claim 1, wherein the method comprises the following steps: In the step 3, erythrocyte membranes and M2 type macrophage membranes are uniformly dispersed in buffer solution with the same pH as that in organisms according to the molar ratio of 1:0.5-2, mixed solution is prepared by normal-temperature ultrasonic treatment and is co-extruded by an extruder to prepare a hybrid membrane, and then the mixed solution is mixed with the drug-loaded black phosphorus nano-sheet prepared in the step 2 according to the molar ratio of 1:0.5-2 and is extruded by the extruder to prepare the bionic nano-particle applied to acute liver injury treatment.
  7. 7. The method for preparing the bionic nano-particles for treating acute liver injury according to claim 4, wherein the method comprises the following steps: the concentration of the black phosphorus nanosheet ethanol suspension in the step 2 is 0.2mg/mL-1mg/mL; The concentration of the urolithin A ethanol solution in the step 2 is 0.5mg/mL-2mg/mL.
  8. 8. A bionic nanoparticle for treating acute liver injury is characterized by being prepared by the preparation method according to any one of claims 1-7.
  9. 9. The bionic nanoparticle for treating acute liver injury according to claim 8, wherein the particle size of the bionic nanoparticle for treating acute liver injury is 100-1000 nm.
  10. 10. Use of the bionic nanoparticle for acute liver injury therapy of claim 8 in preparing a medicament for treating acute liver injury.

Description

Bionic nano-particle applied to acute liver injury treatment and preparation method thereof Technical Field The invention belongs to the field of biological medicine, and in particular relates to bionic nano particles applied to acute liver injury treatment and a preparation method thereof. Background In recent years, drug-Induced Liver Injury (DILI) has gradually replaced alcoholic liver injury, and has become a major cause of acute liver failure. Among the numerous pathogenic drugs, the overdosing of acetaminophen (APAP) is the leading cause. Because APAP is widely used as an over-the-counter antipyretic analgesic, patients are prone to severe hepatotoxicity caused by excessive intake. Currently, the only antidote to treat APAP excess clinically in bulk is N-acetylcysteine (NAC). However, NAC has a narrow therapeutic window and limited efficacy in critically ill or comatose patients. The core mechanism of APAP-induced liver injury is the massive Reactive Oxygen Species (ROS) accumulation initiated by its metabolites. The explosive generation of ROS directly disrupts mitochondrial function, resulting in the opening of mitochondrial permeability transition pores, which in turn trigger massive hepatocyte necrosis. Therefore, a nano delivery system with strong oxidation resistance is developed, high-efficiency removal and targeted intervention of active oxygen are realized, and the method has remarkable clinical significance. Urolithin a (Urolithin A, uroA, C 13H8O4) is a natural polyphenol compound produced by the metabolism of intestinal microorganisms, and precursors thereof are widely found in plants such as pomegranates, blueberries and the like. Studies have shown that UroA has extremely high safety and that direct supplementation with UroA has a much higher bioavailability than ingestion of its precursors by the diet. In the treatment of liver injury UroA exhibits multiple pharmacological activities, which not only directly scavenge chemical free radicals, but also enhance endogenous antioxidant defenses by activating the Nrf2-Keap1 pathway, and also reduce the release of pro-inflammatory cytokines (e.g., TNF- α) by inhibiting the nfkb signaling pathway. However, uroA is limited in its strongly hydrophobic structure and its extremely low solubility makes it possible to administer it only by oral or intraperitoneal injection, resulting in a slow absorption rate in the acute onset phase and a low drug concentration at the target site. In view of the above-mentioned multiple problems, it is currently highly desirable to construct a nano-delivery system that can synergistically enhance its solubility and targeting delivery efficiency and achieve efficient scavenging of active oxygen, so as to break through the limitations of the existing therapies. Disclosure of Invention The invention solves the technical problems that 1, the problem of poor solubility of urolithin A (UroA) is solved, namely, the water solubility of urolithin A is extremely low, so that the bioavailability of urolithin A is poor, and the effective treatment concentration is difficult to be quickly achieved at a target part in the onset period of acute liver injury. 2. Solves the problems of short internal circulation time and poor targeting of the nano particles, that the traditional nano particles are easy to be cleared by an immune system and are difficult to be actively gathered to the inflammation injury part of the liver, thereby limiting the treatment effect of the medicine. 3. Solves the problem that the existing acute liver injury treatment scheme has limited curative effect, has narrow treatment window of clinical medicine N-acetylcysteine (NAC), has poor curative effect on severe patients, and needs to develop a new efficient and safe treatment strategy. In view of the technical problems in the prior art, the preparation method utilizes the nano technology to modify the UroA dosage form so as to improve the solubility and the targeting property of the UroA. The invention designs a bionic nanoparticle applied to acute liver injury treatment and a preparation method thereof. It should be noted that, in the present invention, unless otherwise specified, reference to a specific meaning of "comprising" in the definition and description of compositions includes both open "comprising", "comprising" and the like and closed "consisting of. In order to solve the technical problems, the invention adopts the following scheme: A preparation method of bionic nano-particles applied to acute liver injury treatment comprises the following steps: step 1, preparing black phosphorus nano-sheets; step 2, loading the therapeutic drug on the black phosphorus nano-sheet to prepare a drug-loaded black phosphorus nano-sheet; And 3, coextruding a mixed solution of an erythrocyte membrane and an M2 type macrophage membrane to prepare a hybrid membrane, coating the hybrid membrane on the surface of the drug-loaded black phosphorus nano-sheet prepared in the