Ultrafast charge reversible chitosan-based nanogel as well as preparation method and application thereof

A nano-gel, chitosan technology, applied in the field of biomedicine, can solve the problems of limited delivery and therapeutic effect, achieve long-term stability of charge conversion effect, improve anti-tumor activity, and enhance the effect of accumulation

Active Publication Date: 2021-01-08
XIN HUA HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, size- or charge-reversible processes are often achieved by stimulus-triggered chemical bond breaking, which takes hours, and the nanocarriers may have been cleared before the stimulus-triggered process occurs, limiting delivery and therapeutic efficacy.

Method used

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  • Ultrafast charge reversible chitosan-based nanogel as well as preparation method and application thereof
  • Ultrafast charge reversible chitosan-based nanogel as well as preparation method and application thereof
  • Ultrafast charge reversible chitosan-based nanogel as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 Synthesis and characterization of ultrafast charge-reversal CH-Py-OH NGs

[0049] An effective way to promote the active transport of nanocarriers to tumor sites is through cationic charge-mediated endocytosis and adsorption-mediated transcellular interactions, and designing NGs with fast and efficient cationic charge transfer functions in the acidic tumor microenvironment is key. .

[0050] 1. Experimental steps

[0051] 1.1 Synthesis of ultrafast charge-reversal CH-Py-OH NGs

[0052] To obtain ultrafast pH-triggered charge-reversal NGs with good biocompatibility, CH-Py polymers were first synthesized by chemical oxidative polymerization, and then cross-linked with glutaraldehyde to obtain CH-Py NGs by inverse microemulsion method. ( figure 1 ), and then treat CH-Py NGs (P NGs) with different concentration ratios of NaOH solutions to prepare a series of CH-Py-OH NGs. The specific steps are as follows:

[0053] With 0.1M acetic acid as solvent, prepare an...

Embodiment 2

[0079] Embodiment 2 drug encapsulation and release

[0080] 1. Experimental steps

[0081] 1.1 Encapsulation and release of drugs

[0082] Drug-encapsulated P NGs, R NGs and N NGs using DOX as a model. To evaluate the drug loading efficiency, 5 mg of P NGs, RNGs or N NGs and 1 mg of DOX were soaked in 5 ml of water and stirred for 24 h in the dark. Free DOX was removed by centrifugation (11000 rpm, 10 min) to obtain the final DOX-loaded NGs. In addition, the free DOX concentration in the collected supernatant was measured by UV-vis spectroscopy at 480 nm according to the standard DOX absorption / concentration calibration curve. DOX loading efficiency is estimated by equation (1):

[0083] Drug loading efficiency = (Mo-Mn) / Mo × 100% (1)

[0084] In the formula, Mn and Mo are the supernatant DOX mass and the initial total DOX mass, respectively.

[0085] The kinetics of DOX release from R NGs / DOX in the presence / absence of lysozyme at different pH conditions was studied. R...

Embodiment 3

[0091] Example 3 Cytocompatibility and Cell Internalization

[0092] 1. Experimental steps

[0093] 1.1 Cytocompatibility determination

[0094] A2780 cells at 37 °C and 5% CO 2 Conditions were cultured in DMEM supplemented with FBS (10%, v / v) and penicillin streptomycin (1%, v / v). A2780 cells were treated with different concentrations of P NGs, R NGs and N NGs, and the cell viability was detected by CCK-8 method. Briefly, A2780 cells were seeded in 96-well plates at a density of 6 × 10 3cells were cultured with 200 μl fresh medium for 24 hours, and then the medium in each well was replaced with fresh medium containing P NGs, R NGs or N NGs at different final concentrations (0.05-1 mg / mL). After culturing for 24 h, the culture medium was taken out, and the cells were washed 3 times with phosphate buffered saline (PBS). Add 200 μL of DMEM containing 10% CCK-8 reagent to each well and incubate for 4 h in the dark. The absorbance of each well was measured using a Multiscan ...

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Abstract

The invention provides ultrafast charge reversible chitosan-based nanogel as well as a preparation method and application thereof, and belongs to the field of biomedicine. The preparation method comprises the following steps: synthesizing a chitosan-polypyrrole polymer, then cross-linking the chitosan-polypyrrole polymer with glutaraldehyde to prepare chitosan-polypyrrole nanogel, and finally, treating the chitosan-polypyrrole nanogel with a NaOH solution to obtain a series of chitosan-polypyrrole-hydroxyl nanogel. The prepared ultrafast charge reversible chitosan-based nanogel can realize rapid conversion of pH-induced surface charges, has good cell compatibility, good protein resistance, relatively high anti-cancer drug loading efficiency and relatively good anti-tumor ability, and is hopeful to be used as a safe and promising nano-carrier to construct a low-side-effect enhanced anti-tumor treatment platform, and is applied to the field of biomedicine.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to an ultrafast charge reversible chitosan-based nanogel and a preparation method and application thereof. Background technique [0002] Nanomedicine has emerged as a promising means of delivering diagnostic and therapeutic drugs to solid tumors. However, the drug delivery process needs to go through five steps: 1) blood circulation, 2) accumulation in the tumor, 3) penetration into the tumor tissue, 4) internalization by cancer cells, and 5) intracellular drug release. To a considerable biological barrier, only about 1% of the drug can be delivered to the targeted tumor cells after intravenous injection. This is why many nanocarriers are effective in experimental models, but the results of clinical trials are not satisfactory. [0003] To address the aforementioned biological barrier issues, various nanocarriers with different properties (such as particle size, surface char...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14A61K47/36A61K31/704A61P35/00B82Y5/00
CPCA61K9/146A61K31/704A61P35/00B82Y5/00
Inventor 邢玲溪李鑫史向阳汪希鹏周洁如
Owner XIN HUA HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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