Bacteria-like nano-drug delivery system as well as preparation method and application thereof

A nano-drug and delivery system technology, applied in the directions of drug combination, pharmaceutical formulation, capsule delivery, etc., can solve the problems of weakening the targeting function, difficult to achieve a high level of tumor enrichment, improving the level and limited targeting ability, etc. Improve the effect of recognition and killing, structural stabilization, and tumor growth inhibition

Active Publication Date: 2022-06-28
UNIV OF SCI & TECH OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is difficult to achieve a high level of tumor enrichment with a single drug, and nanocarriers can increase the enrichment of drugs in tumor sites through enhanced penetration and retention effects (EPR effects), but the level of improvement and targeting capabilities are still relatively limited
The targeting of nanocarriers can be enhanced to a certain extent by modifying targeting ligands on the surface of nanocarriers, but the rapid formation of protein coronas on the surface after entering the body significantly weakens its targeting function

Method used

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  • Bacteria-like nano-drug delivery system as well as preparation method and application thereof
  • Bacteria-like nano-drug delivery system as well as preparation method and application thereof
  • Bacteria-like nano-drug delivery system as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment 1 A kind of preparation method of imitating bacteria nanometer drug delivery system

[0044] The preparation method comprises the following steps that are carried out in sequence:

[0045] S1. Preparation of Nanoparticle Concentrates

[0046] To contain 25g PEG 5K -PLGA 11K (biodegradable polymer) and 2.5g (2,3-dioleoyl-propyl)-trimethylamine (cationic lipid) in 0.5L chloroform, add siYthdf1 (siRNA drug) 12.5μmol aqueous solution (25mL), After the first sonication in an ice bath for 1 min, add 5 L of water to the mixture obtained after sonication, place in an ice bath environment, sonicate for the second time for 2 min, suspend and evaporate the chloroform, and concentrate to 0.5 L by ultrafiltration to obtain a nanoparticle concentrate (marker codes are NPs);

[0047] S2. Preparation of bacterial-like nano-drug delivery system

[0048]Preparation of bacterial outer membrane vesicles: Inoculate attenuated Salmonella VNP20009 into LB medium, and shake at ...

Embodiment 2～7

[0050] The preparation method of embodiment 2~7 imitated bacteria nanometer drug delivery system

[0051] Embodiments 2 to 7 are respectively a preparation method of a bacterial-like nano-drug delivery system, and the process steps in their preparation method are similar to those of embodiment 1, and the difference from embodiment 1 is only:

[0052] In Example 2, the biodegradable polymer is PEG 5K -PLA 25K ; siRNA drug is siPd-l1; cationic lipid is BHEM-cholesterol; the ratio of biodegradable polymer, cationic lipid, chloroform, siRNA drug and water is 20g:2g:0.48L:14μmol:4L.

[0053] In Example 3, the biodegradable polymer is PEG 5K -PLA 25K ; siRNA drug is siPd-l1; the ratio of biodegradable polymer, cationic lipid, chloroform, siRNA drug and water is 23g:3g:0.5L:15μmol:5L.

[0054] In Example 4, the siRNA drug was siPd-l1; the ratio of biodegradable polymer, cationic lipid, chloroform, siRNA drug and water was 30g:2.5g:0.4L:12μmol:6L.

[0055] In Example 5, the biode...

Embodiment 8

[0059] Example 8 Performance detection of imitated bacteria nanometer drug delivery system

[0060] (1) Surface potential, particle size and stability of bacterial-like nano-drug delivery systems

[0061] The surface potential, particle size and structural stability of NPs and BNMs were determined by dynamic light scattering.

[0062] The surface potential results of NPs and BNMs are as follows figure 1 As shown, the surface potential of NPs is about 28.33mV, and the surface potential of BNMs is about 26.67mV. particle size such as figure 2 As shown, the particle sizes of both NPs and BNMs are around 180 nm.

[0063] Dynamic light scattering was used to determine the particle stability of NPs and BNMs in physiological solutions (physiological saline containing 2% FBS), such as image 3 As shown, the particle size of NPs and BNMs changed little within 72 h, indicating that the bacterial-like nano-drug delivery system of the present invention has good structural stability i...

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Abstract

The invention belongs to the technical field of drug carriers, and discloses a biomimetic nano-drug delivery system and a preparation method and application thereof.The biomimetic nano-drug delivery system is prepared by mixing bacterial outer membrane vesicles on the basis of a nano-particle concentrated solution prepared from biodegradable polymers, cationic lipid and siRNA drugs and conducting ultrasonic treatment; the preparation method is simple and mild, the raw materials are easy to obtain, the preparation method is suitable for large-scale production, the prepared biomimetic nano-drug carrier is used as an anti-tumor drug, and a constructed drug delivery system is stable in structure, is highly enriched and detained for a long time at a tumor site, can doubly target dendritic cells and tumor cells, and has a good application prospect. The action effect of the anti-tumor medicine is obviously improved.

Description

technical field [0001] The invention belongs to the technical field of drug carriers, and relates to a bacterial-imitation nanometer drug delivery system, in particular to a bacterial-imitation nanometer drug delivery system and a preparation method and application thereof. Background technique [0002] Malignant tumors are one of the intractable diseases that seriously endanger human health. In addition to conventional treatments such as surgery, radiotherapy, and chemotherapy that are commonly used in clinical practice, tumor immunotherapy has shown great potential. Its mechanism is to use the body's immune system to attack tumor cells. . An ideal tumor immunotherapy should at least have the characteristics of high efficiency and low toxicity, that is, to activate the anti-tumor immune response efficiently and achieve effective killing of tumor cells, without causing damage to the normal tissues of the body, or having minimal impact. However, the current tumor immunothera...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/46A61K47/34A61K47/18A61K47/28A61K31/7088A61P35/00
CPCA61K9/5146A61K9/5123A61K9/5192A61K9/5068A61K31/7088A61P35/00Y02A50/30
Inventor 王育才李敏周汉
Owner UNIV OF SCI & TECH OF CHINA
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