Vaccine based on cyclodextrin grafted chitosan, preparation method and application

A technology of cyclodextrin and chitosan, applied in the field of biomedical engineering, can solve problems such as hindering biomedical application and poor solubility, and achieve the effects of good in vivo delivery and antigen storage, good solubility, and improved immune stimulation ability.

Pending Publication Date: 2022-02-01
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, chitosan is only soluble in acidic conditions, but poorly soluble in neutral pH or physiological conditions, which is a major drawback hindering its biomedical applications.

Method used

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  • Vaccine based on cyclodextrin grafted chitosan, preparation method and application
  • Vaccine based on cyclodextrin grafted chitosan, preparation method and application
  • Vaccine based on cyclodextrin grafted chitosan, preparation method and application

Examples

Experimental program
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Effect test

Embodiment 1

[0039] Embodiment 1: synthetic cyclodextrin grafted chitosan (CS-g-CD)

[0040] Synthetic route, see figure 1. β-Cyclodextrin (50.0 g) was dissolved in 200 mL of double-distilled water to obtain a suspension; p-toluenesulfonyl chloride (15.0 g) was then slowly added, and the mixture was stirred at room temperature. After 20% w / v NaOH solution (50 mL) was added to the suspension for 6 hours, the residue was removed by filtration. The pH of the filtrate was adjusted to 7 with dilute hydrochloric acid, and the solution was left at 4°C overnight to obtain a precipitate. The precipitate was filtered and recrystallized to obtain the precipitate, which was lyophilized to obtain β-CD-OTs.

[0041] Chitosan CS (1.00 g) was dissolved in 1% (v / v) acetic acid (80 mL). The N,N-dimethylformamide (DMF, 40mL) solution of β-CD-OTs (1.00-5.00g) was added to the chitosan solution, and cyclodextrins with different grafting degrees were obtained according to different ratios grafted chitosan....

Embodiment 2

[0045] Embodiment 2: the synthesis of MUC1 polypeptide compound

[0046] The synthesis of MUC1 polypeptide compounds is carried out through the solid-phase synthesis strategy proposed by R. Bruce Merrifield. The process is to sequentially link amino acids from the C-terminal to the N-terminal on the solid-phase resin carrier, and finally cut the polypeptide from the solid-phase carrier.

[0047] MUC1, adamantane-modified MUC1 (ada-ACP-MUC1), and adamantane-modified MUC1(Tn) (ada-ACP-MUC1(Tn)) polypeptide compounds (polypeptide structure such as Figure 4 shown). Wherein, ACP is a 6-aminocaproic acid linking arm, and Tn is a glycosylation modification. The specific method of synthesis is as follows:

[0048] 1. Resin swelling, weigh a certain amount of Fmoc-Ala-OH Wang resin (0.05mmol) and place it in a 10mL polypeptide solid-phase synthesis tube, add 6mL N,N-dimethylformamide (DMF) solution, and swell for 3h. Drain the solvent and wash 3 times with DMF and DCM respectively; ...

Embodiment 3

[0055] Example 3 Cyclodextrin-grafted chitosan and MUC1 polypeptide compound (i.e. MUC1 antigen) assembled into nanoparticles

[0056] This embodiment has constructed the vaccine preparation of MUC1 and cyclodextrin grafted chitosan, such as Figure 4 shown. The cyclodextrin-grafted chitosan used in this example is the product 3 with a higher grafting degree, and the grafting degree is 16.69%.

[0057] CS-g-CD and several different MUC1 antigens were further assembled into nanoparticles, that is, cyclodextrin-grafted chitosan (product 3, CS-g-CD) was formulated into a 1 mg / mL solution with acetic acid , then adjust its pH to 4.5 with 0.1M NaOH solution, and stir for 1 h; then, add the above-mentioned polypeptide compounds MUC1, ada-ACP-MUC1, ada-ACP-MUC1 (Tn) respectively, stir at room temperature, and add sodium tripolyphosphate solution ( 1 mg / mL, 0.29 mL), stirred at room temperature for 1 h, and dialyzed for 3 days with a 7000 Da dialysis bag to obtain nanoparticles. de...

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Abstract

The invention discloses a vaccine based on cyclodextrin grafted chitosan (CS-g-CD), a preparation method and application, and belongs to the field of biomedical engineering. Antigen molecules, immunologic stimulants and the like are combined with CS-g-CD in a subject-object self-assembly mode to form supramolecules, and the supramolecules can be further prepared into nano-particles through methods such as sodium tripolyphosphate to serve as vaccine drugs. The cyclodextrin grafted chitosan provided by the invention has better solubility, and the cyclodextrin modified on the cyclodextrin grafted chitosan provides host-guest binding sites, so that the cyclodextrin grafted chitosan can be more easily used for interacting with antigen molecules to form a high-stability self-assembled supramolecular vaccine preparation, and is beneficial to better in-vivo delivery and antigen storage, thereby being beneficial to improving the immune stimulation ability. The vaccine preparation prepared in a subject-object self-assembly mode can be used as a platform for vaccine development, and is suitable for wider vaccine development.

Description

technical field [0001] The invention belongs to the field of biomedical engineering, in particular to a vaccine based on cyclodextrin-grafted chitosan, a preparation method and application. Background technique [0002] Chitosan (CS) is a cationic polysaccharide composed of β(1-4)-linked glucosamine and N-acetylglucosamine, derived from chitin, one of the most abundant polymers in nature, by Obtained by chemical deacetylation. Chitosan has good biocompatibility and biodegradability, and has been widely used in medicine, food, chemical industry, cosmetics and other fields. Chitosan has also been considered as a potential vaccine adjuvant capable of enhancing humoral and cellular immunity. Depending on the degree of deacetylation, chitosan has different amounts of -NH 2 exposed, resulting in an abundance of positive charges. This cationic polysaccharide has the advantage of being easily electrostatically attached to negatively charged cell surfaces, which may play an impor...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/385A61K39/39A61K39/00A61K47/69A61P35/00A61P37/04C08G81/00
CPCA61K39/39A61K39/385A61K39/0011A61K47/6951A61P37/04A61P35/00C08G81/00A61K2039/55583
Inventor 周志昉俞杭艳史哲校屈梦园林汉郑乐乐吴志猛施杰洪皓飞
Owner JIANGNAN UNIV
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