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Preparation of a modified carboxymethyl chitosan nanogel

A technology of carboxymethyl chitosan and methacryloyl carboxymethyl chitosan, applied in the field of preparation of modified carboxymethyl chitosan nanogel, can solve the problem of short half-life in vivo, poor stability, cancer treatment Limited effect and other problems, to achieve the effect of prolonging circulation, preventing protein adsorption, and simple process

Active Publication Date: 2017-05-10
湖南迪斯生物技术股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

As the main means of clinical treatment of tumors, chemotherapy has the disadvantages of lack of selectivity, poor stability, short half-life in vivo and multidrug resistance of anticancer drugs. toxic side effect

Method used

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  • Preparation of a modified carboxymethyl chitosan nanogel
  • Preparation of a modified carboxymethyl chitosan nanogel
  • Preparation of a modified carboxymethyl chitosan nanogel

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Preparation of methacryloyl carboxymethyl chitosan

[0025] Dissolve 1 g of carboxymethyl chitosan in 100 mL of distilled water, stir for 30 minutes in an ice-water bath, then slowly add a certain amount of methacrylic anhydride dropwise, keep stirring mechanically for 24 hours in an ice-water bath, methacryloyl carboxymethyl chitosan The synthetic formula of sugar is shown in Table 1. The reacted product was precipitated with ethanol, and after filtration, the precipitate was washed three times with ethanol, dried in vacuum at 30°C to constant weight, and stored in a -20°C refrigerator. Five methacryloyl carboxymethyl chitosan samples can be obtained by changing the weight ratio of raw materials, as shown in Table 1.

[0026] The synthetic formula of table 1 methacryloyl carboxymethyl chitosan

[0027]

Embodiment 2

[0029] Preparation of nanogels

[0030] Add 80mg of methacryloyl carboxymethyl chitosan and 40mL of distilled water into a 100mL three-necked flask, and stir it magnetically. After it is completely dissolved, add 40mg of N,N-bis(acryloyl)cystamine to the flask, and move the flask into 80 ℃ oil bath, and nitrogen gas was passed into the flask, and after heating for 5 min, 1 mL of potassium persulfate aqueous solution with a concentration of 8 mg / mL was added to the flask, and the reaction was continued at 80 °C for 1 h. The whole reaction process was carried out under the conditions of magnetic stirring and nitrogen protection. Put the reacted nanogel solution into a dialysis bag (MWCO = 8000-14000) and dialyze with distilled water as the dialysis medium for 5 days, and change the dialysis medium every 8 hours to obtain a pure nanogel solution. Using N,N-bis(acryloyl)cystamine to react with CB1, CB2, CB3, CB4, and CB5 respectively, the prepared nanogels were named MCB1, MCB2, ...

Embodiment 3

[0032] pH Sensitivity Analysis of Nanogels

[0033] Use 0.1M NaOH solution and 0.1M HCl solution to adjust the pH of the nanogel solution to 4.5, 5.8, 7.4, and 8.0 respectively. After the pH of the solution is stable, use a ζ potential and a nanoparticle size analyzer to measure the ζ of the nanogel at each pH value. Potential and its particle size. The results are shown in Table 2 and Table 3. It can be seen that as the pH value decreases from 8.0 to 4.5, the zeta potential of the nanogel presents a decreasing trend. This is mainly due to the fact that as the pH value decreases, on the one hand, the particle surface-COO - Gradually transforms into -COOH, on the other hand -NH 2 Transform to positively charged -NH 3 + with-COO - Electrostatic interaction is generated to neutralize the negative charge. These two reasons lead to the -COO on the surface of the nanogel - The amount decreases and the surface charge value decreases. As the pH value decreases from 8.0 to 4.5,...

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Abstract

The invention discloses a preparation method of modified carboxymethyl chitosan nano gel, belonging to the technical field of carriers and sustained-release material. The preparation method comprises the following steps: firstly preparing methylacryloyl carboxymethyl chitosan; and performing free radical polymerization in the presence of N'-N-bis(acrylyl) cystamine serving as a cross-linking agent to prepare the modified carboxymethyl chitosan nano gel. Through determining the particle size and zeta potential of nano particles under the condition of different pH values, the modified carboxymethyl chitosan nano gel is proved to have a pH sensitivity. A protein adsorption test shows that the nano gel is capable of preventing protein adsorption. The prepared nano gel is used for successfully carrying anticancer drug doxorubicin hydrochloride; in-vitro release tests in which PBS solutions different in pH and glutathione concentration are used as media prove that the drug-carried nano particles have relatively good pH and reduction sensitivity.

Description

technical field [0001] The invention belongs to the technical field of carriers and slow-release materials, and relates to a preparation method and application of modified carboxymethyl chitosan nanogel. Background technique [0002] Carboxymethyl chitosan is a water-soluble derivative of chitosan and an amphoteric polyelectrolyte. Because carboxymethyl chitosan has good water solubility, biocompatibility, biodegradability, antibacterial and non-cytotoxic properties, it has been widely used in biomedical fields, such as wound repair, tissue engineering, pharmaceuticals, etc. Delivery, gene therapy, bioimaging, and more. As a drug carrier, carboxymethyl chitosan nanoparticles can improve the stability of the drug, prolong the effective time of the drug, enhance the permeability of the drug to the biomembrane, and eliminate the biological barrier. By controlling the molecular weight and degree of substitution of carboxymethyl chitosan and modifying the carrier to prepare env...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08F251/00C08F222/38C08F220/08C08J3/075A61K47/36A61K9/06A61K31/704
Inventor 倪才华奚林张丽萍石刚
Owner 湖南迪斯生物技术股份有限公司
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