Charge-flipping pullulan derivatives and their synthesis methods and uses

A pullulan polysaccharide and charge inversion technology, applied in the field of charge inversion pullulan polysaccharide derivatives and their synthesis, can solve the problems of lack of tumor targeting and in vivo application limitations, and achieve no immunogenicity and simple synthesis process. , mild conditions

Inactive Publication Date: 2017-11-03
TIANJIN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these positively charged carrier systems have biological safety and stability problems (such as hemolysis, easy uptake by the phagocytic system, etc.), and lack of tumor targeting, so their in vivo applications are greatly limited.

Method used

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  • Charge-flipping pullulan derivatives and their synthesis methods and uses
  • Charge-flipping pullulan derivatives and their synthesis methods and uses
  • Charge-flipping pullulan derivatives and their synthesis methods and uses

Examples

Experimental program
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Embodiment 1

[0048] 1. Synthesis of diethylenetriamine-modified pullulan (AMPL) (e.g. figure 1 )

[0049] Dissolve 500 mg pullulan (molecular weight 200 kDa) and 500 mg N,N'-carbonyldiimidazole (CDI) in 20 ml of anhydrous dimethyl sulfoxide (DMSO) and stir for 5-10 min, then add 1- 2 ml / min was slowly dropped into 10 ml of DMSO solution in which 2 ml of diethylenetriamine was dissolved, and the reaction was stirred at 35°C for 20 h. After the reaction, the reaction solution was transferred to a dialysis bag (molecular weight cut-off 12-14 kDa), dialyzed in ultrapure water for 3 days, and the dialysate was freeze-dried for 40 hours. The white flocculent product obtained was AMPL. The degree of substitution of the polyamino-modified group can be calculated by detecting the content of nitrogen element by means of elemental analysis, which is 15.7%.

[0050] 2. Synthesis of cis-4-cyclohexene-1,2-dicarboxylic acid monoamidation-diethylenetriamine-modified pullulan (CAPL) (e.g. figure 1 ). ...

Embodiment 2

[0075] 1. Synthesis of spermine-modified pullulan (SPL)

[0076] Dissolve 500 mg pullulan (molecular weight 200 kDa) and 500 mg N,N'-carbonyldiimidazole (CDI) in 20 ml of anhydrous dimethyl sulfoxide (DMSO) and stir for 5-10 min, then add 1- 2 ml / min was slowly dropped into 10 ml of DMSO solution dissolved with 5 ml of spermine, and the reaction was stirred at 35°C for 24 h. After the reaction, the reaction solution was transferred to a dialysis bag (molecular weight cut-off 12–14 kDa), dialyzed in ultrapure water for 3 days, and the dialysate was freeze-dried for 40 hours. The white flocculent product obtained was SPL. The degree of substitution of the spermine-modified group was 37.9%.

[0077] 2. Synthesis of maleic acid monoacylation-spermine modified pullulan (MSPL)

[0078] Dissolve 200 mg of the above SPL in 10 ml DMSO, add 100 mg maleic anhydride and stir for 24 h, then pour the reaction solution into cold ethanol solution, a white flocculent precipitate is precipi...

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Abstract

The invention relates to a charge reversal Pulullan derivative and a synthesis method and application thereof. The Pulullan derivative is composed of a Pulullan framework, a multi-amino modified group and a beta-carboxylic acid amide modified group, has remarkable liver / liver cancer targeting property, and can quickly respond to a faintly acid tumor microenvironment and a cell endosome / lysosome so as to achieve reversal from electronegativity to electropositivity. By modifying poly(beta-amino ester) (PBAE) / polylactic acid-polyglycolic acid copolymer (PLGA) composite nanoparticles with the Pulullan derivative, liver cancer targeted delivery of nanoparticles can be mediated efficiently, effective release of a carried drug at the tumor position is achieved, and the charge reversal Pulullan derivative is a liver / liver cancer targeted carrier material with excellent performance for drugs, genes and image contract agents and has broad application space.

Description

technical field [0001] The invention relates to a charge-reversal pullulan derivative and its synthesis method and application. Specifically, it is prepared by modifying pullulan with polyamino compounds, and introducing pH-sensitive β-carboxylic acid amide bonds through the reaction of terminal amino groups with phthalic anhydrides. Pullulan derivatives have liver / liver cancer targeting properties, can quickly respond to the weakly acidic tumor microenvironment and cell endosomes / lysosomes, and realize the reversal from negative to positive, and can be used as drugs, genes The invention relates to a liver / liver cancer targeting carrier material of an imaging contrast agent, belonging to the technical field of biochemical medicine. Background technique [0002] Biomedical polymer materials are an important part of biomaterials and have been widely used in the field of medicine, such as diagnosis and treatment of diseases, replacement or repair of damaged tissues and organs,...

Claims

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Application Information

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Patent Type & AuthorityPatents(China)
IPC IPC(8): C08B37/02A61K47/36A61K9/14A61K49/00A61P35/00A61P1/16
CPCA61K9/145A61K47/36A61K49/00C08B37/0018
Inventor王银松张聪安彤王丹
OwnerTIANJIN MEDICAL UNIV