Carboxymethyl chitosan quaternary ammonium salt/PAMAM(Polyamidoamine) core-shell nanoparticles and preparation method

Abstract

The invention discloses carboxymethyl chitosan quaternary ammonium salt / PAMAM(Polyamidoamine) core-shell nanoparticles and a preparation method. The nanoparticles are chitosan derivatives which are formed in a way that amino-terminated polyamidoamine dendritic macromolecule is grafted with carboxymethyl chitosan quaternary ammonium salt, and the chitosan derivatives are self-aggregated to form core-shell nanoparticles in water solution. The preparation method comprises the following steps: performing quaterisation decoration to amino at a second position of chitosan by CTA (3-Chloro-2-hydroxypropyltrimethyl ammonium chloride); performing carboxymethyl decoration to hydroxy at a sixth position of chitosan quaternary ammonium salt to synthetize carboxymethyl chitosan quaternary ammonium salt; activating carboxyl of the carboxymethyl chitosan quaternary ammonium salt by using NHS(N-Hydroxysuccinimide) / EDC(carbodiimide) to link the amino-terminated polyamidoamine dendritic macromolecule to synthetize the dendritic chitosan derivatives. The preparation process condition is simple and mild, and the product is easy to purify; and the core-shell nanoparticles of the prepared dendritic chitosan derivatives have the advantages of excellent water-solubility and functionality and has the attractive application prospect in the fields of antibiosis, gene transfer and drug controlled release.

Description

technical field

[0001] The present invention relates to a kind of carboxymethyl chitosan quaternary ammonium salt / polyamide-amine dendritic macromolecule core-shell nanoparticle and its preparation method, more specifically refers to carboxymethylated chitosan quaternary ammonium salt graft end The invention discloses core-shell nanoparticles of amino polyamide-amine dendritic macromolecules (PAMAM) and a preparation method thereof, belonging to the field of functional polymer materials. Background technique

[0002] Chitosan is the only natural alkaline polysaccharide. It is only soluble in dilute acid solutions with pH<6.5, but it is difficult to dissolve in water and alkaline solutions. The introduction of different groups into the molecular chain of chitosan can improve the water solubility of chitosan on the one hand, and more importantly, the introduction of different groups will endow chitosan with more functions. Therefore, chemical modification of chitosan is t...

Examples

Embodiment 1

[0041] 4g chitosan (molecular weight: 200,000, degree of deacetylation: 80%) is suspended in 40ml of isopropanol, slowly add 24ml of NaOH solution with a mass fraction of 40% under stirring, heat up to 60°C, and basify with stirring at 600 rpm 4h. Then, 128 ml of 69% (w / v) CTA aqueous solution was slowly added dropwise, and after 60 minutes of completion of the dropwise addition, the temperature was raised to 80° C., and the reaction was stirred for 9 hours. After the reaction was finished, the filtered reaction product was dialyzed in deionized water for 72 hours, freeze-dried to obtain N-(2-hydroxypropyl)trimethylammonium chloride chitosan, and the degree of quaternization substitution was 74%.

[0042] Suspend 4 g of the N-(2-hydroxypropyl)trimethylammonium chloride chitosan in 30 ml of NaOH solution with a mass fraction of 50%, and basify overnight at -20°C. Then the chitosan quaternary ammonium salt after alkalization was moved in 90ml isopropanol. At room temperature, ...

Embodiment 2

[0047] The preparation process of N-(2-hydroxypropyl)trimethylammonium chloride-O-carboxymethyl chitosan and compound 2 is the same as that of Example 1.

[0048] Under the protection of nitrogen in an ice-water bath at 2°C, 4 g of compound 2 was dissolved in 40 ml of anhydrous methanol under stirring at 800 rpm in the dark, and a methanol solution with a concentration of 0.1 g / ml of compound 2 was prepared. 11.2 ml of methyl acrylate was dissolved in 20 ml of anhydrous methanol under stirring in an ice-water bath, and then slowly dropped into the methanol solution of compound 2. After the dropwise addition was completed for 30 minutes, the mixture was stirred and reacted at 35° C. in the dark for 24 hours. After the reaction, unreacted methyl acrylate and methanol were removed by rotary evaporation at 50° C. to obtain 1.5-generation polyamide-amine dendrimers with ethylenediamine as the core.

[0049] In an ice-water bath at 2°C, under nitrogen protection, and under stirring...

Embodiment 3

[0052] The preparation process of N-(2-hydroxypropyl)trimethylammonium chloride-O-carboxymethyl chitosan is the same as in Example 1.

[0053] Add 5.0 g of ammonia to 120 ml of absolute ethanol in an ice-water bath at 2° C. under nitrogen protection and stirring at 800 rpm to obtain a methanol solution with a concentration of 0.04 g / ml of ammonia. 90 g of methyl acrylate was dropped into the methanol solution of ammonia within 100 min. Afterwards, the reaction was stirred for 36 h at 25° C. in the dark. After the reaction, unreacted methyl acrylate and methanol were removed by rotary evaporation at 50° C. to obtain 0.5-generation polyamide-amine dendrimers with ammonia as the core.

[0054] In an ice-water bath at 2°C, under nitrogen protection, under stirring at 800 rpm in the dark, dissolve the 2.0 g of 0.5 generation polyamide-amine dendrimer with ammonia as the core in 20 ml of methanol solution, and then slowly drop into 100g ethylenediamine. After the dropwise additio...

technical field

[0001] The present invention relates to a kind of carboxymethyl chitosan quaternary ammonium salt / polyamide-amine dendritic macromolecule core-shell nanoparticle and its preparation method, more specifically refers to carboxymethylated chitosan quaternary ammonium salt graft end The invention discloses core-shell nanoparticles of amino polyamide-amine dendritic macromolecules (PAMAM) and a preparation method thereof, belonging to the field of functional polymer materials. Background technique

[0002] Chitosan is the only natural alkaline polysaccharide. It is only soluble in dilute acid solutions with pH<6.5, but it is difficult to dissolve in water and alkaline solutions. The introduction of different groups into the molecular chain of chitosan can improve the water solubility of chitosan on the one hand, and more importantly, the introduction of different groups will endow chitosan with more functions. Therefore, chemical modification of chitosan is t...

Examples

Embodiment 1

[0041] 4g chitosan (molecular weight: 200,000, degree of deacetylation: 80%) is suspended in 40ml of isopropanol, slowly add 24ml of NaOH solution with a mass fraction of 40% under stirring, heat up to 60°C, and basify with stirring at 600 rpm 4h. Then, 128 ml of 69% (w / v) CTA aqueous solution was slowly added dropwise, and after 60 minutes of completion of the dropwise addition, the temperature was raised to 80° C., and the reaction was stirred for 9 hours. After the reaction was finished, the filtered reaction product was dialyzed in deionized water for 72 hours, freeze-dried to obtain N-(2-hydroxypropyl)trimethylammonium chloride chitosan, and the degree of quaternization substitution was 74%.

[0042] Suspend 4 g of the N-(2-hydroxypropyl)trimethylammonium chloride chitosan in 30 ml of NaOH solution with a mass fraction of 50%, and basify overnight at -20°C. Then the chitosan quaternary ammonium salt after alkalization was moved in 90ml isopropanol. At room temperature, ...

Embodiment 2

[0047] The preparation process of N-(2-hydroxypropyl)trimethylammonium chloride-O-carboxymethyl chitosan and compound 2 is the same as that of Example 1.

[0048] Under the protection of nitrogen in an ice-water bath at 2°C, 4 g of compound 2 was dissolved in 40 ml of anhydrous methanol under stirring at 800 rpm in the dark, and a methanol solution with a concentration of 0.1 g / ml of compound 2 was prepared. 11.2 ml of methyl acrylate was dissolved in 20 ml of anhydrous methanol under stirring in an ice-water bath, and then slowly dropped into the methanol solution of compound 2. After the dropwise addition was completed for 30 minutes, the mixture was stirred and reacted at 35° C. in the dark for 24 hours. After the reaction, unreacted methyl acrylate and methanol were removed by rotary evaporation at 50° C. to obtain 1.5-generation polyamide-amine dendrimers with ethylenediamine as the core.

[0049] In an ice-water bath at 2°C, under nitrogen protection, and under stirring...

Embodiment 3

[0052] The preparation process of N-(2-hydroxypropyl)trimethylammonium chloride-O-carboxymethyl chitosan is the same as in Example 1.

[0053] Add 5.0 g of ammonia to 120 ml of absolute ethanol in an ice-water bath at 2° C. under nitrogen protection and stirring at 800 rpm to obtain a methanol solution with a concentration of 0.04 g / ml of ammonia. 90 g of methyl acrylate was dropped into the methanol solution of ammonia within 100 min. Afterwards, the reaction was stirred for 36 h at 25° C. in the dark. After the reaction, unreacted methyl acrylate and methanol were removed by rotary evaporation at 50° C. to obtain 0.5-generation polyamide-amine dendrimers with ammonia as the core.

[0054] In an ice-water bath at 2°C, under nitrogen protection, under stirring at 800 rpm in the dark, dissolve the 2.0 g of 0.5 generation polyamide-amine dendrimer with ammonia as the core in 20 ml of methanol solution, and then slowly drop into 100g ethylenediamine. After the dropwise additio...

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