CN-121971648-A - Drug-loaded microalgae motor and preparation method and application thereof

Abstract

The invention relates to the technical field of micro-nano, and discloses a drug-loaded microalgae motor, a preparation method and application thereof. The microalgae motor loaded with the drugs comprises the microalgae motor and nanoparticle drugs loaded on the microalgae motor, wherein the microalgae motor is connected with the nanoparticle drugs through electrostatic adsorption, the microalgae is natural or engineered unicellular algae with movement capability, and the nanoparticle drugs are formed by self-assembly after covalent cross-linking of natural polysaccharide and natural active substances. The invention utilizes the self flagella movement of the microalgae, and the microalgae motor can move autonomously in the gastrointestinal tract and actively target to the colon inflammation part, thereby improving the local concentration of the medicine and enhancing the curative effect. The microalgae motor combines the powerful antioxidant/anti-inflammatory activity of astaxanthin with the biological activity of microalgae, and can synergistically relieve colonitis in multiple ways.

Inventors

• LI HONGYAN
• GONG XINWEI
• GU YUCHAO
• LI HUIRU
• ZHANG CHUQIAO
• CHE HONGXIA

Assignees

• 青岛科技大学

Dates

Publication Date

20260505

Application Date

20260107

Claims (10)

1. 1. A microalgae motor loaded with a drug is characterized by comprising a microalgae motor and a nanoparticle drug loaded on the microalgae motor, wherein the microalgae motor is connected with the nanoparticle drug through electrostatic adsorption, the microalgae is natural or engineered unicellular algae with movement capability, and the nanoparticle drug is formed by self-assembling natural polysaccharide and natural active substances after covalent crosslinking.
2. 2. The drug-loaded microalgae motor according to claim 1, wherein the unicellular algae is one or more of Chlamydomonas reinhardtii, spirulina, chlorella, and Euglena.
3. 3. The drug-loaded microalgae motor of claim 1, wherein the natural active substance is one or more of astaxanthin, fucoxanthin and lycopene.
4. 4. The drug-loaded microalgae motor of claim 1, wherein the natural polysaccharide is selected from one or more of chitosan and its derivatives, dextran and its derivatives, hyaluronic acid and its derivatives, algin and its derivatives, pectin and its derivatives, and cyclodextrin and its derivatives.
5. 5. The drug-loaded microalgae motor of claim 1, wherein the nanoparticle drug is formed by reacting natural polysaccharide with natural active substance to generate Schiff base, performing covalent crosslinking, and then self-assembling in an aqueous phase system.
6. 6. A method of preparing the microalgae motor of claim 1, comprising the steps of: (1) Dissolving natural polysaccharide in a buffer solution, adding a catalyst and ethylenediamine, then adding an organic solvent containing natural active substances, stirring and reacting for 24-72 hours under the conditions of protecting gas atmosphere and light shielding, and dispersing in the buffer solution after dialysis, concentration and freeze drying to form a dispersion liquid, and filtering by a microporous filter membrane to obtain functionalized nano particles; (2) Culturing microalgae to logarithmic growth phase, and centrifugally collecting microalgae cells; (3) Dispersing the functionalized nano particles obtained in the step (1) in a culture medium, then adding the microalgae cells obtained in the step (2) into the culture medium, incubating for 5-15 minutes at room temperature, and centrifuging to obtain a precipitate, namely the microalgae motor.
7. 7. The method of claim 6, wherein the buffer solution in the step (1) is acetate buffer solution or phosphate buffer solution, the pH value is 5.0-5.5, the protective gas is nitrogen, the reaction temperature is 30-70 ℃, the dialysis molecular weight cut-off is 3500-Da, the dialysis time is 24-72 h, the catalyst is NHS and EDC, the molar ratio of the natural polysaccharide to the natural active substance is 1:1, the molar ratio of the natural polysaccharide to the catalyst is 10:0-5, the molar ratio of the NHS to the EDC is 1:2-4, and the molar ratio of the natural polysaccharide to the ethylenediamine is 10-5:0-1.
8. 8. The method of claim 6, wherein the centrifugal speed in the step (2) is 300-700 rpm, and the centrifugal time is 1-10 minutes.
9. 9. The method of claim 6, wherein the medium in the step (3) is SE medium, the volume ratio of the functionalized nanoparticles to the medium is (0.5-1) to 2, and the concentration of the microalgae cells in the medium is 0.5X10 7 /mL.
10. 10. Use of a drug-loaded microalgae motor of any of claims 1-5 in the preparation of a colitis targeted therapeutic drug.

Description

Drug-loaded microalgae motor and preparation method and application thereof Technical Field The invention relates to the technical field of micro-nano, in particular to a drug-loaded microalgae motor and a preparation method and application thereof. Background Intestinal diseases such as chronic colitis, inflammatory Bowel Disease (IBD), irritable Bowel Syndrome (IBS), etc. have become global health problems. These diseases are often accompanied by pathological features such as oxidative stress, impaired intestinal barrier function, over-expression of inflammatory factors, and dysregulation of intestinal flora. At present, clinical treatment mainly comprises anti-inflammatory drugs, immunosuppressants and biological agents, but has the problems of poor targeting property, large side effect, easy recurrence and the like. Natural active ingredients such as astaxanthin, curcumin, resveratrol and the like show a broad prospect in the field of intestinal health due to the strong antioxidant and anti-inflammatory activities. Astaxanthin (AST) is one of the strongest antioxidants in nature, and is effective in scavenging free radicals, enhancing intestinal barrier function and regulating flora structure. However, the natural active ingredients have the defects of poor water solubility, low chemical stability and easy oxidative degradation, and are easily damaged by gastric acid and digestive enzymes in the gastrointestinal tract digestion process, so that the bioavailability is extremely low, and the practical application of the natural active ingredients in the fields of biological medicines, foods and the like is severely limited. Microalgae have self-propulsion, good biocompatibility and low toxicity, and are ideal biological driving carriers. Microalgae can realize autonomous movement through flagella swing, can actively migrate in complex biological environments such as gastrointestinal tract and the like, and is expected to improve the delivery efficiency of drugs at target sites. In addition, part of microalgae have certain biological activity, can regulate the immune function of organisms, improve the intestinal flora structure and generate synergistic treatment effect with the loaded active ingredients. However, how to load nano-drugs on microalgae efficiently, and utilize the motility of the nano-drugs to realize targeted treatment of colonitis lesions, and at the same time, overcome the influence of gastric acid environment on the activity of microalgae is a technical problem to be solved urgently. Therefore, development of the microalgae motor with the functions of autonomous movement capability, gastric acid stability, colon targeting and multiple treatments has important significance for improving the curative effect of the active ingredients and expanding the application range of the active ingredients. Disclosure of Invention The invention aims to overcome the defects in the prior art and provides a microalgae motor loaded with medicines, and a preparation method and application thereof. In order to achieve the aim, the technical scheme of the invention is that the microalgae motor loaded with the drugs comprises the microalgae motor and nanoparticle drugs loaded on the microalgae motor, wherein the microalgae motor is connected with the nanoparticle drugs through electrostatic adsorption, the microalgae is natural or engineered unicellular algae with movement capability, and the nanoparticle drugs are formed by self-assembly after covalent cross-linking of natural polysaccharide and natural active substances. Further, the unicellular algae is one or more of chlamydomonas reinhardtii, spirulina, chlorella and euglena. Further, the natural active substance is one or more of astaxanthin, fucoxanthin and lycopene. Further, the natural polysaccharide is selected from one or more of chitosan and its derivatives, dextran and its derivatives, hyaluronic acid and its derivatives, algin and its derivatives, pectin and its derivatives, cyclodextrin and its derivatives. The nanoparticle medicine is formed by performing Schiff base reaction on natural polysaccharide and natural active substances, performing covalent crosslinking, and then performing self-assembly in an aqueous phase system. The other technical scheme of the invention is that the method for preparing the microalgae motor comprises the following steps: (1) Dissolving natural polysaccharide in a buffer solution, adding a catalyst and ethylenediamine, then adding an organic solvent containing natural active substances, stirring and reacting for 24-72 hours under the conditions of protecting gas atmosphere and light shielding, and dispersing in the buffer solution after dialysis, concentration and freeze drying to form a dispersion liquid, and filtering by a microporous filter membrane to obtain functionalized nano particles; (2) Culturing microalgae to logarithmic growth phase, and centrifugally collecting microalgae cells; (3) Dispersing the func