Folic acid modifying chitosan nano particles as well as preparation and application thereof

A technology of chitosan nano and chitosan, which is applied in the direction of medical preparations of non-active ingredients, capsule delivery, antineoplastic drugs, etc., can solve the problems of poor selective metabolism, low molecular weight dispersion width, etc., and achieve mild experimental conditions , low dispersion width, and good pH sensitivity

Inactive Publication Date: 2018-11-23
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by the present invention is to provide a folic acid-modified chitosan nanoparticle and its preparation and application, which overcomes the defects of poor cell selection and metabolism of existing composite nanomaterials, and the method is simple to operate and has mild reaction conditions , and the molecular weight dispersion width of the obtained product FA-CS-g-PNIPAM is low, and the particle size of chitosan polymer nanoparticles is about 200nm, which can reach breast cancer to the greatest extent and be selectively metabolized by specific tissues or cells

Method used

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  • Folic acid modifying chitosan nano particles as well as preparation and application thereof
  • Folic acid modifying chitosan nano particles as well as preparation and application thereof
  • Folic acid modifying chitosan nano particles as well as preparation and application thereof

Examples

Experimental program
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Embodiment 1

[0035] (1) Synthesis of CS-g-PNIPAM: Dissolve 5g chitosan CS in 250mL 1% acetic acid solution, stir to dissolve completely, slowly add 250mL methanol and stir until clear, then dropwise add 1mL acetic anhydride solution, stir at room temperature After reacting for 3.5 hours, add 10% NaOH solution to precipitate chitosan in the solution, filter and dry to obtain acetylated chitosan, and grind it into a fine powder for later use. Dissolve 0.298 g of the obtained acetylated chitosan in 5 mL of DMF and stir to dissolve, add 0.370 g of DDACT, 0.015 g of DMAP, and 0.205 g of DCC, stir and react at room temperature for 48 hours, pour ice water into the ice water bath overnight, and use a dialysis bag with MWCO=3500 for three dialyses. days, and then lyophilized to obtain the RAFT reagent of chitosan. Dissolve 0.047g of the obtained chitosan RAFT reagent in 5mL DMF, stir magnetically for 4.5h under a nitrogen atmosphere to dissolve completely, add 0.0016g AIBN as an initiator, 0.5g NI...

Embodiment 2

[0041] (1) Synthesis of CS-g-PNIPAM: Dissolve 5g chitosan CS in 250mL 1% acetic acid solution, stir to dissolve completely, slowly add 250mL methanol and stir until clear, then dropwise add 1mL acetic anhydride solution, stir at room temperature After reacting for 3.5 hours, add 10% NaOH solution to precipitate chitosan in the solution, filter and dry to obtain acetylated chitosan, and grind it into a fine powder for later use. Dissolve 0.298 g of the obtained acetylated chitosan in 5 mL of DMF and stir to dissolve, add 0.370 g of DDACT, 0.015 g of DMAP, and 0.205 g of DCC, stir and react at room temperature for 48 hours, pour ice water into the ice water bath overnight, and use a dialysis bag with MWCO=3500 for three dialyses. days, and then lyophilized to obtain the RAFT reagent of chitosan. Dissolve 0.047g of the obtained chitosan RAFT reagent in 5mL of DMF, stir magnetically for 4.5h under a nitrogen atmosphere to dissolve completely, add 0.0032g of AIBN as an initiator, a...

Embodiment 3

[0044] Using DOX as the model drug, prepare the drug-loaded composite material FA-CS-g-PNIPAM / DOX, dissolve FA-CS-g-PNIPAM in water, add doxorubicin DOX, stir the reaction, dialyze, and freeze-dry to obtain folic acid-modified Chitosan nano drug-loaded composite material FA-CS-g-PNIPAM / DOX; wherein the mass ratio of DOX to FA-CS-g-PNIPAM is 1:2~5 and the drug release test is carried out under different pH conditions:

[0045] Weigh 2 mg of the drug-loaded complex FA-CS-g-PNIPAM / DOX and fully dissolve in pure water, put them into two dialysis bags (MW=3500) respectively, place them in the dissolution apparatus, and add 20ml of PBS solution respectively (pH=7.4) and acetic acid solution (pH=5.0), the temperature of the dissolution apparatus was set at 37°C, and the rotation speed was 90 rpm, respectively at 2h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h, 60h, After 72 hours, 1ml of dialysate was taken out, and 1ml of corresponding PBS buffer solution and acetate buffer solution were re...

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Abstract

The invention relates to folic acid modifying chitosan nano particles as well as preparation and application thereof. The preparation method comprises the following steps: adding folic acid FA, EDC and NHS into a solvent, stirring, and obtaining a mixed solution; and adding the mixed solution into a prepared aqueous solution of chitosan temperature-sensitive segmented copolymer CS-g-PNIPAM, stirring, dialyzing, and freeze drying, thus obtaining the folic acid modifying chitosan nano particles. By adopting the RAFT method, the reaction is stable, no implosion occurs, and a reaction product is low in molecular weight dispersion width.

Description

technical field [0001] The invention belongs to the field of composite nanomaterials and their preparation and application, in particular to a folic acid-modified chitosan nanoparticle and its preparation and application. Background technique [0002] As a natural cationic polysaccharide, chitosan has a wide range of sources and is relatively cheap, non-toxic, has good biocompatibility and biodegradability, and can be widely used in the fields of medicine, food and chemical industry. But chitosan also has many deficiencies. There are hydrogen bonds between chitosan molecules to make chitosan high in crystallinity, so it is insoluble in general organic solvents, which greatly limits the application of chitosan. So the research on the modification of chitosan came into being and made a lot of progress. At present, with the development of controlled / living free radical polymerization in the synthesis of macromolecules with clear structure and controllable molecular weight, the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/36A61K47/54A61P35/00
CPCA61K9/5161A61K47/545A61P35/00
Inventor 朱利民钱倩倩牛世伟章学易
Owner DONGHUA UNIV
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