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Chitosan nano drug carrier with pH and temperature response and preparation method and application thereof

A nano-drug carrier, chitosan nano technology, applied in the direction of drug combination, pharmaceutical formula, non-active ingredient medical preparations, etc., can solve the problem of external signal stimulation, reduce toxic side effects, mild conditions, and improve bioavailability degree of effect

Inactive Publication Date: 2018-05-11
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The invention solves the technical problem that the drug carrier in the prior art causes drug burst release and needs external signal stimulation to respond, and provides a chitosan nano drug carrier with dual response to pH and temperature

Method used

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  • Chitosan nano drug carrier with pH and temperature response and preparation method and application thereof
  • Chitosan nano drug carrier with pH and temperature response and preparation method and application thereof
  • Chitosan nano drug carrier with pH and temperature response and preparation method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0033] Preparation of solid cyclodextrinized chitosan nanoparticles with pH / temperature dual response

[0034] (1) Synthesis of cyclodextrinized chitosan (CS-g-CD): Weigh 2g of chitosan (deacetylation degree 95%, viscosity average molecular weight 100,000) and dissolve it in 100mL 1% acetic acid aqueous solution (pH~ 5.6) to obtain a chitosan solution with a concentration of 2% (w / v); weigh 2g of carboxymethylated cyclodextrin and dissolve it in 50mL of deionized water to obtain a cyclodextrin with a concentration of 4% (w / v) solution; add 2g 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and 1g N-hydroxysuccinimide (NHS ), stirring and reacting at room temperature for 2 h to activate the carboxyl group of the cyclodextrin derivative to obtain an activated cyclodextrin solution. The activated cyclodextrin solution is fully mixed with the chitosan solution, stirred and reacted at room temperature for 24 hours, the cyclodextrin carboxylated derivative is modifi...

Embodiment 2

[0038] Preparation of Hollow Cyclodextrinized Chitosan Nanoparticles Responsive to pH / Temperature

[0039] Based on Example 1, the difference is: modify the preparation process of the TPP solution described in step (2) of Example 1 to: dissolve 8 mg of TPP in 20 mL of deionized water to obtain a 0.4 mg / mL TPP solution, and the rest Steps are all the same as in Example 1.

[0040] The cyclodextrinized chitosan nanoparticles prepared in this example are as follows: figure 2 As shown, it is a hollow spherical particle with an average diameter of about 250nm, wherein the chitosan modified by TPP cross-linking forms a hollow hydrophobic core, and the hydrophilic cyclodextrin groups are closely arranged side by side to form a shell. Compared with the solid cyclodextrinized chitosan nanoparticles prepared in Example 1, the hydrophobic core of the nanoparticles prepared in this example is a hollow structure, which may be because the ions of TPP and chitosan in this example The reas...

Embodiment 3

[0042] Preparation of cyclodextrinized chitosan nanoparticles loaded with doxorubicin and pH / temperature dual response

[0043] Dissolve 1 mg of doxorubicin hydrochloride in 5 mL of N,N-dimethyloxalamide (DMF), add 2 μL of triethylamine to desalt the doxorubicin hydrochloride to obtain a solution with a concentration of 0.2 mg / mL of doxorubicin, and dissolve the The drug solution was stirred and mixed with the cyclodextrinized chitosan solution (20 mL, 0.4 mg / mL) described in step (2) in Example 1 for 2 hours to obtain a cyclodextrinized chitosan solution containing doxorubicin. Adopt the preparation method of the cyclodextrinized chitosan nanoparticle described in embodiment 1 step (2), add TPP solution, stirring reaction, filter respectively in the described cyclodextrinized chitosan solution containing doxorubicin , that is, cyclodextrinized chitosan nanoparticles loaded with doxorubicin and pH / temperature dual response are obtained, and the drug is loaded in the cavity of ...

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Abstract

The invention provides a chitosan nano drug carrier with pH and temperature response and a preparation method and application thereof. The nano drug carrier is of a core-shell structure, a core of thecore-shell structure is formed through ionic crosslinking of chitosan and sodium tripolyphosphate, and a shell is formed by accumulation of carboxyl derivative of cyclodextrin. The preparation methodcomprises the steps of activation of the carboxyl derivative of the cyclodextrin, synthesis of cyclodextrinated chitosan and preparation of cyclodextrinated chitosan nano particles. According to thechitosan nano drug carrier, hydrophobic drugs are carried to the nano particles through hydrophobic interaction, and the nano particle drug carrier has dual responsiveness to the pH and the temperature, and can be used for targeted drug delivery to improve utilization rate of the drugs.

Description

technical field [0001] The invention belongs to the field of nano-medicine, and in particular relates to a cyclodextrinized chitosan nano-medicine carrier with dual response to pH / temperature and a preparation method thereof. Background technique [0002] Chitosan is the product of deacetylation of chitin. It is the only alkaline polysaccharide among natural polysaccharides. It has good biocompatibility, degradability and modifiability, so it is widely used in the field of biomedicine. every aspect. Chitosan-based amphiphilic nano-drug carriers can effectively solve the problems of low solubility, poor absorption, and low bioavailability of antitumor drugs. The commonly used methods for preparing amphiphilic chitosan nanoparticles include covalent modification-self-assembly method and ionic cross-linking-self-assembly method. For example, Ma Xiaojun et al. reported that chitosan was modified with lipophilic small molecule lithocholic acid to obtain an amphiphilic chitosan ...

Claims

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Application Information

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IPC IPC(8): A61K47/40A61K47/36A61K45/00A61P35/00
Inventor 杨光肖林黄丽霞周凤吴丹
Owner HUAZHONG UNIV OF SCI & TECH
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