Nano drug delivery system based on p-coumaric acid polymer and preparation method and application thereof

A technology of p-coumaric acid and polymers, which is applied in the direction of pharmaceutical formulations, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems that coumaric acid has not been reported, and achieve bioavailability Excellent degradability and biocompatibility, short reaction cycle and good reproducibility

Pending Publication Date: 2019-10-08
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, more and more studies focus on the anti-tumor effect of p-coumaric acid, but the

Method used

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  • Nano drug delivery system based on p-coumaric acid polymer and preparation method and application thereof
  • Nano drug delivery system based on p-coumaric acid polymer and preparation method and application thereof
  • Nano drug delivery system based on p-coumaric acid polymer and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0072] The preparation of embodiment 1 polymer PCA

[0073] 1, the preparation method of polymer PCA, comprises the following steps:

[0074] Add 10 mL of organic solvent pyridine into a 50 mL round-bottomed flask and pre-cool in an ice bath at 0°C for 5 min, then add 0.4 mL (6 mmol) of SOCl dropwise 2 , after stirring at 300rpm for 10min, add 3mmol of p-coumaric acid powder, remove the ice bath after the powder is dissolved, and continue to react at room temperature for 1h; Then resuspended in 0.01M dilute hydrochloric acid and sonicated for 15 minutes, then repeatedly washed with ultrapure water and freeze-dried to obtain a reddish-brown polymer product, which is polymer PCA; the molecular weight of polymer PCA is 2000-5000.

[0075] The organic solvent pyridine in the preparation raw materials can be replaced by other organic solvents, such as acetone, methanol, triethylamine, tetrahydrofuran or dimethylformamide, etc., wherein the polymer PCA prepared by using the basic o...

Embodiment 2

[0079] Example 2 Preparation of a polymer PCA-based DTX@PCA NPs nano drug delivery system

[0080] 1. Preparation of DTX@PCA NPs nano drug delivery system, including the following steps:

[0081] (1) Polymer PCA, hydrophobic antineoplastic drug - docetaxel (DTX) and DSPE-PEG (PEG molecular weight 2000-3000) were dissolved in the solvent dimethyl sulfoxide (DMSO) respectively, and prepared 10mg / mL solution, and then mixed according to the volume ratio of 5:1:3, and the content of DSPE-PEG was controlled to be 50% of the total content of polymer PCA and DTX; the organic phase was obtained;

[0082] (2) Add 0.6mL of the organic phase dropwise to 6mL of ultrapure water under stirring at a stirring speed of 1000rpm; after the addition, continue to stir for 30s, then transfer the nanoparticle solution to an ultrafiltration tube with a molecular weight cut-off of 100000, Centrifuge at 3000rpm for 15min and repeat twice to obtain nanoparticles loaded with drug DTX (DTX@PCA NPs), whic...

Embodiment 3

[0087] Example 3 In vitro anti-tumor activity of nano drug delivery system (DTX@PCA NPs)

[0088] The in vitro anti-tumor activity of the nano drug delivery system DTX@PCA NPs prepared in Example 2 was tested by MTT method.

[0089] 1. Method

[0090] Mouse colorectal cancer cells (CT26 cells) were inoculated in 96-well plates at a density of 5000 cells / well, cultured overnight, discarded the culture medium and added fresh culture medium containing different concentrations of drug-loaded nanoparticles (DTX@PCA NPs) After 24 hours, add MTT and incubate for 4 hours, then discard the medium and add DMSO to fully dissolve the crystals, and finally use a microplate reader to measure the absorbance of each well at 490 nm and calculate the cell viability.

[0091] 2. Results

[0092] Figure 5 It is the cancer cell activity after different concentrations of common docetaxel (DTX) and drug-loaded nanoparticles DTX@PCA NPs cultured for 24 hours. Depend on Figure 5 It can be seen ...

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Abstract

The invention discloses a nano drug delivery system based on a p-coumaric acid polymer and a preparation method and an application thereof. The method synthesizes a biocompatible and biodegradable polymer PCA by a solution polycondensation method by using natural phenolic acid and p-coumaric acid as monomers; and based on the polymer PCA, the PCA nano drug delivery system is prepared by a nanoprecipitation method. The system is uniform in size and stable in nature, and can effectively load hydrophobic anticancer drugs and improve their bioavailability, significantly enhances the anti-tumor treatment effect in vitro and in vivo, and reduces the toxic side effects of the drug. In addition, a polymer carrier itself also exhibits certain anti-tumor activity, which can help enhance the efficacyof anti-cancer drugs, and opens up a new way for the application of p-coumaric acid in anti-tumor. The preparation method of the polymer and the nano-drug delivery system thereof have the advantagesof easy reaction operation, less reaction steps, short reaction period and high repeatability.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials. More specifically, it relates to a p-coumaric acid polymer-based nano drug delivery system and its preparation method and application. Background technique [0002] Cancer has become one of the leading causes of death worldwide. It is predicted that there will be 21 million new cancer cases and 13.2 million deaths in 2030. Currently, chemotherapy is still one of the main treatments for cancer. However, chemotherapy drugs generally have defects such as large toxic side effects, multidrug resistance, and low bioavailability, which seriously affect the quality of life of patients and greatly limit clinical applications. The main reason for the low bioavailability of chemotherapeutic drugs is that most chemotherapeutic drugs are hydrophobic drugs, which are difficult to prepare into suitable dosage forms, and various excipients such as latent solvents and co-solvents are often used to...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K31/765A61K47/34A61P35/00C08G63/08C08G63/87
CPCA61K9/5153A61K31/765A61P35/00C08G63/08C08G63/823
Inventor 吴钧王丽英游欣如黄丽萍
Owner SUN YAT SEN UNIV
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