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CN-121987818-A - CALPEPTIN magnetic nano drug-loaded particles for targeted enrichment of medium membrane layer and application thereof

CN121987818ACN 121987818 ACN121987818 ACN 121987818ACN-121987818-A

Abstract

The invention relates to CALPEPTIN magnetic nano drug-loaded particles for targeted enrichment of a medium membrane layer and application thereof, and belongs to the technical field of biological medicine. The invention designs CALPEPTIN magnetic nano drug-carrying particles of a targeting medium membrane layer, the CALPEPTIN magnetic nano drug-carrying particles of the invention adopt a core-shell structure, a magnetic core is composed of superparamagnetic ferroferric oxide nano particles, the core endows a material with response capability to an external magnetic field, a polymer shell layer is formed by wrapping Polydopamine (PDA) on the surface of the magnetic core, and CALPEPTIN is covalently connected to a polydopamine shell. The CALPEPTIN magnetic nano drug-loaded particles solve the technical problem that the composite material cannot penetrate through the aortic wall efficiently and is specifically enriched in the medium membrane layer, thereby providing a reliable directional intervention scheme with in-vivo experimental evidence support for the accurate treatment of TAAD.

Inventors

  • WU WEIHUA
  • XU JINGCHENG
  • YANG YUNLIN
  • WANG SHINING
  • TENG XIAOMEI

Assignees

  • 苏州大学

Dates

Publication Date
20260508
Application Date
20260104

Claims (10)

  1. 1. The CALPEPTIN magnetic nano drug-loaded particle targeting the medium membranous layer is characterized in that the CALPEPTIN magnetic nano drug-loaded particle comprises a superparamagnetic ferroferric oxide nano particle, a polydopamine shell coating the superparamagnetic ferroferric oxide nano particle, and CALPEPTIN covalently connected to the polydopamine shell.
  2. 2. The method for preparing CALPEPTIN magnetic nano-drug-loaded particles as defined in claim 1, comprising the steps of: S1, mixing superparamagnetic ferroferric oxide with dopamine for reaction to obtain Fe 3 O 4 @PDA nanoparticles; and S2, incubating CALPEPTIN with Fe 3 O 4 @PDA nanoparticles to obtain the magnetic nano drug-carrying particles.
  3. 3. The method of claim 2, wherein the mass ratio of Fe 3 O 4 @PDA nanoparticles to CALPEPTIN is (1-2).
  4. 4. The method according to claim 2, wherein in the step S2, the co-incubation is performed under a dark condition, and the temperature of the co-incubation is 1-10 ℃.
  5. 5. The method according to claim 2, wherein in step S1, the pH of the reaction is 7.5 to 9.
  6. 6. Use of CALPEPTIN magnetic nano-drug-loaded particles according to claim 1 or CALPEPTIN magnetic nano-drug-loaded particles prepared by the method of any one of claims 2-5 in the preparation of aortic aneurysm/interlayer therapeutic drugs.
  7. 7. A therapeutic drug for aortic aneurysm/dissection, comprising CALPEPTIN magnetic nano-drug-loaded particles according to claim 1 or CALPEPTIN magnetic nano-drug-loaded particles prepared by the preparation method according to any one of claims 2 to 5.
  8. 8. The therapeutic agent according to claim 7, wherein the dosage form of the therapeutic agent comprises a tablet, powder, suspension, granule, capsule, injection, spray, solution, enema, emulsion, film, suppository, patch, nasal drop or drop pill.
  9. 9. The therapeutic agent of claim 7, wherein the route of administration of the therapeutic agent comprises intravenous injection, intraperitoneal injection, intramuscular injection, subcutaneous injection, oral administration, sublingual administration, nasal administration, or transdermal administration.
  10. 10. Use of CALPEPTIN magnetic nano-drug-loaded particles as defined in claim 1 or CALPEPTIN magnetic nano-drug-loaded particles as defined in any one of claims 2 to 5 in the manufacture of an aortic aneurysm/interlayer treatment device, characterized in that the treatment device further comprises means capable of dispersing a magnetic field.

Description

CALPEPTIN magnetic nano drug-loaded particles for targeted enrichment of medium membrane layer and application thereof Technical Field The invention relates to the technical field of biological medicine, in particular to a preparation method and application of CALPEPTIN magnetic nano medicine-carrying particles of a targeting enrichment medium membrane layer. Background Thoracic aortic aneurysm/dissection (TAAD) is a critical condition of aortic intimal tearing leading blood to enter the media layer to form dissection hematoma, and is a cardiovascular disease with extremely high illness and death rate. Current treatment strategies mainly include open surgery and endoluminal repair, however these methods are traumatic, severe in indication, and lack effective early intervention. Drug therapy is often performed by systemic administration, for example, by direct administration of CALPEPTIN inhibitors themselves. CALPEPTIN as a cell permeable Calpain protease inhibitor, are administered systemically by intravenous or intraperitoneal injection in animal models. However, the method adopts systemic administration, the medicine is distributed to all tissues and organs of the whole body along with blood circulation, and effective enrichment can not be realized at specific lesion sites (such as thoracic aortic aneurysm/aortic wall of interlayer). This results in insufficient local drug concentration in the lesion, while other normal tissues are exposed to the drug, with a high risk of off-target effects. Due to the lack of targeting of drugs, which are widely distributed throughout the systemic circulation, higher single-dose doses must be administered in order to achieve effective therapeutic concentrations at the focal site. In addition, calpain inhibitors are metabolically unstable in vivo and have a short half-life and require frequent dosing to maintain effective drug concentrations in the blood, which not only reduces patient compliance, but also presents difficulties in long-term treatment management. In recent years, development of nanomedicine and targeted delivery technology has provided new ideas for TAAD treatments. The paper by Doi No. 10.7150/thno.109325 indicates that NPCAs nanoparticles of sizes 80 nm, 150 nm and 240 nm are all able to cross the damaged endothelial barrier and achieve significant enrichment of the membranous layer in the aorta, thus enabling deep delivery of Calpain inhibitors using the nanoparticles. For example, therapeutic agents such as Calpain inhibitors are entrapped in liposomes or polymeric nanoparticles (e.g., PLGA). After intravenous injection, the nano particles circulate along with blood, and as the permeability of the diseased aortic vessel wall increases, the particles can be passively enriched in the focus area to a certain extent, so that certain directional administration is realized. However, the technology utilizes the enhanced permeability and retention effect (EPR effect) to realize the enrichment of the nano particles in the focal zone, is greatly dependent on the pathological state of the focal zone, has large individual difference and limited enrichment degree, and cannot realize the accurate and efficient enrichment of the medicine. It is difficult to penetrate into the lesion core that passive targeting is primarily dependent on leaking blood vessels, and for treatments requiring action on the tunica media in the aorta, the simple EPR effect is difficult to ensure effective penetration and accumulation of the drug in the critical structures. There is therefore a need to further refine the delivery effect of nanoparticles on Calpain inhibitors in order to achieve their deep targeting. Disclosure of Invention Therefore, the invention aims to solve the technical problem that the drug-loaded nano particles in the prior art are difficult to penetrate through the middle membrane layer so as to not realize deep targeting of the drug. In order to solve the technical problems, the invention provides a preparation method and application of CALPEPTIN magnetic nano drug-loaded particles for targeted enrichment of a medium membrane layer. The middle aortic membrane layer consists of tens of layers of elastic fibers, collagen and smooth muscle cells which are annularly arranged, has compact and elastic structure and is a core for maintaining the structural integrity of the aortic wall. TAAD the core pathological process (such as smooth muscle cell apoptosis and elastic fiber rupture) occurs precisely in the medium layer. However, due to the compact structure of the middle membrane layer, a general drug carrying system cannot enter the middle membrane layer. Therefore, the invention designs CALPEPTIN magnetic nano drug-carrying particles of the targeting medium membrane layer, the CALPEPTIN magnetic nano drug-carrying particles of the invention adopt a core-shell structure, a magnetic core is composed of superparamagnetic ferroferric oxide nano particles, and the core endow