Mannose-modified thiolated chitosan quaternary ammonium salt nanoparticle, preparing method and application thereof

A technology of thiolated chitosan and chitosan quaternary ammonium salt, which is applied in the field of nanoparticles, can solve the problems of inability to effectively improve the uptake of small intestinal epithelial cells, lack of targeting specific groups, lower absorption and transfection efficiency, etc. problems, to achieve the effect of improving cell adhesion, increasing affinity, and increasing oral bioavailability

Inactive Publication Date: 2012-03-21
FUDAN UNIV
View PDF2 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, because it does not have a targeting specific group, it cannot more effectively improve the uptake of small intestinal epithelial cells, M cells and macrophages located in Peyer's nodes in the small intestine, reducing absorption and transfection efficiency, thereby limiting its use as an oral delivery carrier. effective use

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Mannose-modified thiolated chitosan quaternary ammonium salt nanoparticle, preparing method and application thereof
  • Mannose-modified thiolated chitosan quaternary ammonium salt nanoparticle, preparing method and application thereof
  • Mannose-modified thiolated chitosan quaternary ammonium salt nanoparticle, preparing method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Example 1 Preparation of mannose-modified chitosan quaternary ammonium salt-cysteine

[0058] TMC was synthesized according to the method reported in the literature (Eur J Pharm Biopharm 2004,57:77-83). The weight average molecular weight of chitosan was 30 kDa, and the reaction time was 45 min, 120 min and 180 min, respectively. The degree of quaternization of TMC was respectively 15%, 30% and 60%. Cl - Purified by anion-exchange resin, freeze-dried; weighed 400 mg TMC dissolved in 160 mL water, 400 mg mannopyranyl isothiocyanate dissolved in 40 mL dimethyl sulfoxide (DMSO), mixed, adjusted to pH 8.5 , reacted at room temperature for 6 h, ultrafiltered (MWCO 10 kDa), and the obtained Man-TMC was freeze-dried; weighed 160 mg Man-TMC dissolved in 8 mL water, 5 mg cysteine ​​was dissolved in 2 mL water, mixed, and added to the final The concentrations of EDAC and NHS were 50 mM, adjusted to pH 5.0, and reacted at room temperature for 5 h. The reaction product was dialyz...

Embodiment 2

[0059] Example 2 Preparation of mannose-modified chitosan quaternary ammonium salt-cysteine

[0060] TMC was synthesized according to the method reported in the literature (Eur J Pharm Biopharm 2004,57:77-83). The weight average molecular weight of chitosan was 100 kDa, and the reaction time was 45 min, 120 min and 180 min, respectively. 15%, 30% and 60%. Cl - Purified by anion-exchange resin, freeze-dried; weighed 400 mg TMC dissolved in 160 mL water, 400 mg mannopyranyl isothiocyanate dissolved in 40 mL dimethyl sulfoxide (DMSO), mixed, adjusted to pH 9.0 , reacted at room temperature for 12 h, ultrafiltered (MWCO 10 kDa), and the obtained Man-TMC was freeze-dried; weighed 125 mg Man-TMC dissolved in 8 mL water, 5 mg cysteine ​​was dissolved in 2 mL water, mixed, and added to the final The concentrations of EDAC and NHS were 100 mM, adjusted to pH 3.0, and reacted at room temperature for 2 h. The reaction product was dialyzed against pH 5.0 HCl solution (MWCO 3500 Da) at 4...

Embodiment 3

[0061] Example 3 Preparation of mannose-modified chitosan quaternary ammonium salt-cysteine

[0062] TMC was synthesized according to the method reported in the literature (Eur J Pharm Biopharm 2004,57:77-83). The weight average molecular weight of chitosan was 200 kDa, and the reaction time was 45 min, 120 min and 180 min, respectively. The quaternization degrees of TMC were respectively 15%, 30% and 60%. Cl - Purified by anion-exchange resin, freeze-dried; Weigh 400 mg TMC dissolved in 160 mL water, 400 mg mannopyranyl isothiocyanate dissolved in 40 mL dimethyl sulfoxide (DMSO), mix, adjust pH to 9.5 , reacted at room temperature for 24 h, ultrafiltered (MWCO 10 kDa), and the obtained Man-TMC was freeze-dried; weighed 100 mg Man-TMC dissolved in 8 mL water, 5 mg cysteine ​​dissolved in 2 mL water, mixed, and added to the final The concentrations of EDAC and NHS were 200 mM, adjusted to pH 4.0, and reacted at room temperature for 8 h. The reaction product was dialyzed again...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
molecular weightaaaaaaaaaa
particle sizeaaaaaaaaaa
particle diameteraaaaaaaaaa
Login to view more

Abstract

The present invention belongs to the technical field of nanoparticle, and particularly relates to a mannose-modified thiolated chitosan quaternary ammonium salt nanoparticle, a preparation method and application thereof. The nanoparticle of the invention is generated through polyelectrolyte effect between mannose-modified thiolated chitosan quaternary ammonium salt with positive charges and mannose-modified thiolated chitosan quaternary ammonium salt with negative charges. Simultaneously the nanoparticle loads protein peptide medicine or nucleic acid medicine with negative charges, wherein the mannose-modified thiolated chitosan quaternary ammonium salt is obtained from amino-groups of the chitosan through quaternizing, mannose ligand and sulfhydrylation modification successively. The nanoparticle has the following advantages: no requirement for organic solvent in preparation process, and effectively improved medicine stability. The nanoparticle can actively target intestinal epithelial cells, M cells and macrophages. Intestinal absorption for the oral medicine and transfection efficiency of the nucleic acid medicine are effectively improved. The effect of the mannose-modified thiolated chitosan quaternary ammonium salt nanoparticle is much better than that of the prior-art chitosan nanoparticle.

Description

technical field [0001] The invention belongs to the technical field of nanoparticles, and in particular relates to a mannose-modified thiol chitosan quaternary ammonium salt nanoparticle and a preparation method and application thereof. Background technique [0002] Nanoparticles refer to solid colloidal particles with a particle size between 10-1000 nm, which can improve the solubility and stability of drugs, prolong the circulation time in the body, and have good slow and controlled release effects. They have been widely used in protein peptide drugs and Nucleic acid drug delivery system. The prior art discloses a variety of nanoparticle preparation methods, including solvent evaporation, surface polymerization, emulsion polymerization and other methods to prepare nanoparticles. The organic solvents used, heating and severe mechanical action may cause the activity of biomacromolecular drugs to decrease or even Inactivate. Positively charged polymers and negatively charge...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/36A61K9/14
Inventor 印春华唐翠何春柏殷黎晨
Owner FUDAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap