CN-121987589-A - Scutellarin-loaded brain tissue exosome nano-particles and application thereof in preparing medicines for treating diseases by penetrating blood brain barrier

Abstract

The invention relates to brain tissue exosome nano-particles loaded with scutellarin and application thereof in preparing medicines for treating diseases by penetrating blood brain barrier, belonging to the technical field of medicines, wherein the brain tissue exosome nano-particles loaded with scutellarin are added into mouse microglial cells, astrocytes and brain microvascular endothelial cells to obtain microglial cell polarization which is caused by PRV infection and can be regulated, so that the expression of M1 microglial cell CD86 is obviously inhibited, the expression of M2 microglial cell CD 206 is promoted, and the anti-inflammatory effect is exerted; the brain delivery efficiency of scutellarin can be enhanced by the brain tissue exosome obtained by the in vitro Transwell blood brain barrier and living brain tissue model exosome penetration blood brain barrier test. The scutellarin-loaded brain tissue exosome nano-particles solve the problem of difficult penetration of the scutellarin blood brain barrier and low bioavailability, and have important practical significance for prevention and control of porcine pseudorabies.

Inventors

• SHU XIANGHUA
• SONG CHUNLIAN
• ZHANG YING
• LI TING
• PAN DENG
• LI YUEYAN
• ZHANG DEGUI
• LI HONGXIA

Assignees

• 云南农业大学
• 昆明伟牧得生物科技有限公司

Dates

Publication Date

20260508

Application Date

20260128

Claims (7)

1. 1. The brain tissue exosome nano-particle loaded with scutellarin is characterized in that the particle size of the exosome-scutellarin nano-particle is 100+/-15 nm, and the drug loading rate of the scutellarin is 31.86+/-2.5 ng Scu/mug exosome.
2. 2. A method of preparing nanoparticles according to claim 1, comprising the steps of: (1) Diluting brain tissue exosomes with PBS, adding scutellarin, and performing ultrasonic treatment; (2) Incubating; (3) Centrifuging and discarding the supernatant; (4) Adding PBS for resuspension to obtain exosome-scutellarin.
3. 3. The preparation method according to claim 2, wherein 1mL PBS dissolves 20 mg scutellarin, the brain tissue exosomes are diluted to 500 μl with PBS, and 0.8 mg scutellarin is added.
4. 4. Use of the nanoparticle according to claim 1 for the preparation of a medicament for the treatment of a disease by penetration of the blood brain barrier.
5. 5. The use according to claim 4, wherein the disease is a PRV-induced neuroinflammatory disorder of the brain or microglial polarization.
6. 6. Use of the nanoparticle of claim 1 for the preparation of a medicament for the treatment of a related neuroinflammatory disorder by targeting the brain.
7. 7. A pharmaceutical composition for treating a disease associated with PRV comprising the scutellarin-loaded brain tissue exosome nanoparticle of claim 1.

Description

Scutellarin-loaded brain tissue exosome nano-particles and application thereof in preparing medicines for treating diseases by penetrating blood brain barrier Technical Field The invention belongs to the technical field of medicines, and in particular relates to a scutellarin-loaded brain tissue exosome nanoparticle and application thereof in preparing a medicament for treating diseases by penetrating through blood brain barrier. Background Pseudorabies virus (Pseudorabies virus, PRV) belongs to the family porcine herpesviridae, members of which are capable of infecting almost humans and all kinds of animals. After infection of adult pigs by PRV, the virions typically become latent in the peripheral ganglion of the host. PRV can break the host blood brain barrier leading to damage to brain tissue, causing neurological symptoms such as mental confusion, intense itching, skin crumbling, and even death. Microglia, which act as resident immune cells within the central nervous system, play a vital role in maintaining the integrity of the Blood Brain Barrier (BBB) and play an immunoregulatory role in the repair process following brain damage. Aiming at the pathogenesis of PRV, a substance which has the characteristics of high efficiency crossing the blood brain barrier, brain tissue targeting and natural homing to specific cells (such as microglial cells) in the brain is urgently needed, and the treatment effect on PRV-induced lower nervous system diseases is improved. The BBB is a highly selective permeability barrier that functions to effectively isolate the Central Nervous System (CNS) from the peripheral blood circulation, defend the brain from toxins and pathogens, tightly regulate the CNS microenvironment, and ensure proper neuronal function. The barrier also eliminates more than 98% of small molecule drug candidates and almost all macromolecular drugs, becoming the primary rate limiting factor for drug entry into the CNS. The nano drug delivery system can promote the drug to penetrate the BBB without damaging the BBB, and is a method for preventing and treating CNS diseases. Exosomes (exosomes) are a class of extracellular vesicles with diameters between 30 and 150 nanometers, which mediate unique intercellular communication and interaction functions, allowing sorting and transport of substances within cells. The function of the exosome is closely related to the cell type from which the exosome is derived, and the exosome has the capability of naturally targeting cells or organs, and the exosome realizes the transfer of the content of the exosome to the cytoplasm of the target cell through the ligand-receptor interaction of the surface molecule and the receptor of the target cell, endocytosis or direct fusion with the target cell membrane, thereby completing the targeting delivery function. Exosomes derived from the nervous system play an important role in regulating neurological diseases. The exosome has the advantages of high stability in body fluid, strong targeting of tissues or cells, good biocompatibility, no toxicity, no clearance by immune system and the like, and becomes a loading system for conveying therapeutic drugs, thereby realizing targeted therapy of the drugs. Erigeron breviscapus (Breviscapine) is also called erigeron breviscapus, asarum herb, erigeron breviscapus, etc., and is a dried whole herb of erigeron breviscapus (Erigeron breviscapus (vant.) hand-Mazz) of Compositae. The traditional Chinese medicine composition is mainly applied to treating cardiovascular and cerebrovascular diseases clinically. Scutellarin (Scu) as a representative component of scutellarin flavonoids, whose content exceeds 90% is a key component of scutellarin that exerts main efficacy in treating cerebrovascular diseases, and can protect neurons from ischemic injury by anti-inflammatory, anti-apoptotic and antioxidant activities. However, scutellarin has limited efficacy in entering the human body. Disclosure of Invention Based on the problems set forth in the background technology, the invention provides the brain tissue exosome nano-particles loaded with scutellarin, and the high drug loading rate is realized by an ultrasonic drug loading method, so that the BBB penetration rate and brain targeting of scutellarin are obviously improved. The nanoparticle can be specifically ingested by microglia, and can relieve neuroinflammation by inhibiting M1 type polarization and promoting M2 type polarization of microglia induced by PRV, thereby providing a new therapy for central nervous system diseases and providing technical support for preventing and controlling PRV diseases. Based on the above, a first object of the present invention is to provide a scutellarin-loaded brain tissue exosome nanoparticle having a particle size of 100±15 nm and a drug loading rate of 31.86±2.5 ng Scu/. Mu.g exosome. A second object of the present invention is to provide a method for preparing the above nanoparticle, comprising the steps