CN-121971652-A - Chitosan oligosaccharide-based piceatannol nano delivery particles, and preparation method and application thereof

Abstract

The invention belongs to the technical field of biological pharmacy, and provides a white piceatannol nano delivery particle based on chitosan oligosaccharide, and a preparation method and application thereof. The piceatannol nano delivery particles are chitosan oligosaccharide nano drug-carrying particles modified by hyaluronic acid and D-tyrosine, and the chitosan oligosaccharide nano drug-carrying particles comprise chitosan oligosaccharide nano particle carriers and piceatannol wrapped in the chitosan oligosaccharide nano particle carriers. The chitosan oligosaccharide nano drug-carrying particles are subjected to functional modification by adopting the hyaluronic acid and the D-tyrosine, the hyaluronic acid realizes targeted delivery to an MRSA infection part, the D-tyrosine has the biological membrane dispersing capability, damages a biological membrane structure, promotes the drug to penetrate into the biological membrane deeper and improve the MRSA infection resistance effect, enhances the antibacterial and anti-biological membrane activity of piceatannol on the MRSA, shows stronger antibacterial capability, can obviously reduce the bacterial load of the lung, relieves inflammatory lung injury, and enhances the treatment effect of resisting the MRSA infection.

Inventors

• BAI YUBIN
• GAO XUN
• ZHOU XUZHENG
• CHENG FUSHENG
• Li Jiehang
• LI BING
• HU RONGBIN
• ZHANG JIYU
• WEI XIAOJUAN
• WANG WEIWEI
• ZHOU YAXIN
• Zhai Bintao

Assignees

• 中国农业科学院兰州畜牧与兽药研究所

Dates

Publication Date

20260505

Application Date

20260309

Claims (10)

1. 1. The white piceatannol nano delivery particles based on chitosan oligosaccharide are characterized in that the white piceatannol nano delivery particles are chitosan oligosaccharide nano drug-carrying particles modified by hyaluronic acid and D-tyrosine; The chitosan oligosaccharide nanoparticle drug-loading particles comprise a chitosan oligosaccharide nanoparticle carrier and piceatannol wrapped in the chitosan oligosaccharide nanoparticle carrier.
2. 2. The chitosan oligosaccharide-based piceatannol nano-delivery particle according to claim 1, wherein the particle size of the piceatannol nano-delivery particle is 230-270 nm, and the particle size of the chitosan oligosaccharide nano-drug-carrying particle is 190-210 nm.
3. 3. The method for preparing chitosan oligosaccharide-based piceatannol nano-delivery particles as claimed in claim 1 or 2, comprising the steps of: 1) Mixing the piceatannol solution, the chitosan oligosaccharide solution and the sodium tripolyphosphate solution, and performing cross-linking to obtain chitosan oligosaccharide nano drug-carrying particles; 2) And adding the activated hyaluronic acid solution into chitosan oligosaccharide nano drug-loaded particles, performing coupling reaction, and then adding D-tyrosine solution for reaction to obtain chitosan oligosaccharide-based piceatannol nano delivery particles.
4. 4. The method according to claim 3, wherein the concentration of the chitosan oligosaccharide solution in the step 1) is 1-3 mg/mL, the concentration of the sodium tripolyphosphate solution is 0.5-1.5 mg/mL, and the concentration of the piceatannol solution is 0.5-1.5 mg/mL; The volume ratio of the chitosan oligosaccharide solution to the sodium tripolyphosphate solution is 5-8:1; the volume ratio of the piceatannol solution to the chitosan oligosaccharide solution is 1:4-10.
5. 5. The method according to claim 3 or 4, wherein the crosslinking temperature in step 1) is 20-30 ℃ and the crosslinking time is 5-15 min.
6. 6. The method according to claim 5, wherein the concentration of the hyaluronic acid solution in step 2) is 0.5-1.5 mg/mL, and the concentration of the D-tyrosine solution is 1-3 mg/mL.
7. 7. The preparation method of claim 6, wherein the volume ratio of the hyaluronic acid solution in step 2) to the chitosan oligosaccharide solution in step 1) is 1:38-43, and the volume ratio of the D-tyrosine solution in step 2) to the chitosan oligosaccharide solution in step 1) is 1:1-3.
8. 8. The method of preparation according to claim 6 or 7, wherein the reagent used for the activation in step 2) comprises 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide; the activation temperature is 35-40 ℃, and the activation time is 2-4 hours.
9. 9. The preparation method according to claim 8, wherein the temperature of the coupling reaction in the step 2) is 35-40 ℃, and the time of the coupling reaction is 20-26 hours; The temperature of the reaction in the step 2) is 35-40 ℃, and the reaction time is 2-4 hours.
10. 10. Use of the chitosan oligosaccharide-based piceatannol nano-delivery particles of claim 1 or 2 in the preparation of an anti-MRSA drug.

Description

Chitosan oligosaccharide-based piceatannol nano delivery particles, and preparation method and application thereof Technical Field The invention relates to the technical field of biological pharmacy, in particular to a white piceatannol nano delivery particle based on chitosan oligosaccharide, and a preparation method and application thereof. Background Staphylococcus aureus (Staphylococcus aureus) is a common opportunistic pathogen of human and animal co-occurrence and can cause various diseases including skin infection, abscess, impetigo, necrotizing pneumonia, septicemia, catheter-related endocarditis, osteomyelitis and the like. Methicillin-resistant staphylococcus aureus (MRSA) is a multi-resistant pathogen evolving from staphylococcus aureus, and is known for multiple resistance, high infection rate and high mortality rate, and poses serious challenges for clinical treatment. Furthermore, the ability of MRSA to form biofilms protects bacteria from host immune defenses and antibiotic therapy, thereby significantly increasing the complexity of infection management, which leads to persistent infections and vicious circle of increased medical costs, making clinical treatment exceptionally difficult, there is a need to develop simpler, more efficient synthetic strategies and safer antimicrobial agents against MRSA. Currently, antibiotics are the primary strategy for treating bacterial infections. However, the long-term and unreasonable use of antibiotics leads to the emergence of bacterial resistance, and the emergence of multi-and pan-resistant bacteria constitutes a serious threat to public health and safety. In this context, natural compounds are receiving considerable attention due to their diverse antimicrobial mechanisms, low potency to induce drug resistance, and multi-target pharmacological properties. Piceatannol (PIC), a structural analog of resveratrol, is commonly found in blueberries, grapes and passion fruit seeds and has a variety of biological activities including antibacterial, anti-inflammatory and antioxidant effects. The anti-inflammatory effects of PICs are mediated primarily by inhibition of key pro-inflammatory factors (such as TNF- α and IL-6), highlighting their therapeutic potential in a variety of pathologies, including liver injury, heart injury, cancer and skin disease. PICs have been shown to inhibit MRSA growth and biofilm formation. However, the clinical application of PICs is limited by their low solubility, poor bioavailability, and insufficient specificity for pathogen targeting. Thus, improving the solubility, bioavailability, and clinical efficacy of PIC formulations remains an important focus of current research. The nano particles have small particle size, large specific surface area, unique physical and chemical properties and enhanced reactivity, and have great application prospects in the aspect of disease treatment. In recent years, nanocarriers have become one of the most promising drug delivery systems. Among the many nanocarriers, chitosan Oligosaccharide (COS) is a natural cationic polymer, and is an ideal candidate material because it is easily prepared into nanoparticles (COS-NPs), and has excellent biocompatibility, inherent antibacterial activity, and potential active targeting ability against bacteria. These properties enable COS-NPs to reduce the required drug dose and to improve the overall antimicrobial efficacy. However, the main limitation of COS-NPs is that their surface carries a strong positive charge, which, while favoring their interaction with bacteria, promotes electrostatic adhesion to negatively charged biofilm matrix, thus causing the nanoparticles to be trapped, impeding their penetration deep, and limiting the removal of the biofilm. Therefore, the research uses chitosan oligosaccharide nano-particles as a carrier of piceatannol to establish a pathogen-responsive drug delivery mechanism acting on an MRSA infection site, and has important significance for anti-MRSA drugs. Disclosure of Invention The invention aims to provide a white piceatannol nano delivery particle based on chitosan oligosaccharide, and a preparation method and application thereof. In order to achieve the above object, the present invention provides the following technical solutions: The invention provides a chitosan oligosaccharide-based piceatannol nano delivery particle, which is a chitosan oligosaccharide nano drug-carrying particle modified by hyaluronic acid and D-tyrosine; The chitosan oligosaccharide nanoparticle drug-loading particles comprise a chitosan oligosaccharide nanoparticle carrier and piceatannol wrapped in the chitosan oligosaccharide nanoparticle carrier. Preferably, the particle size of the piceatannol nano delivery particles is 230-270 nm, and the particle size of the chitosan oligosaccharide nano drug-carrying particles is 190-210 nm. The invention also provides a preparation method of the chitosan oligosaccharide-based piceatannol nano delivery p