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An anti-tumor drug-resistant nano-delivery system encapsulating two surfactants and preparation method thereof

A drug-loaded nanotechnology, anti-tumor technology, applied in the field of medicine, can solve the problems of inability to improve the water solubility of nanoparticles, ineffective reversal of MDR, and no resistance to resistance. Medicinal effect, low cost effect

Active Publication Date: 2017-08-01
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

(5) Deletion of apoptotic genes or overexpression of anti-apoptotic genes can lead to tumor cell resistance to chemotherapeutic drugs
However, F68 itself has no ability to resist drug resistance
Therefore, the drug efficacy of reversing MDR containing F68 nanoparticles is not obvious
However, L61, which has a strong anti-drug resistance ability, cannot improve the shortcomings of poor water solubility and low stability of nanoparticles due to its strong hydrophobicity.

Method used

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  • An anti-tumor drug-resistant nano-delivery system encapsulating two surfactants and preparation method thereof
  • An anti-tumor drug-resistant nano-delivery system encapsulating two surfactants and preparation method thereof
  • An anti-tumor drug-resistant nano-delivery system encapsulating two surfactants and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Embodiment 1: Preparation of drug-loaded nanoparticles

[0055] Dissolve 1mg DTX (Shanghai Sangon Bioengineering Co., Ltd.) with 5mg F68 and 10mg L61 and 20mg PCL (US Sigmaaldrich Company) in 1ml dichloromethane, ultrasonically dissolve to make an organic phase; 50 mg emulsifier cholic acid Sodium (Shanghai Sangon Bioengineering Co., Ltd.) was dissolved in 5ml of water to make the aqueous phase. Add the organic phase to the water phase, and ultrasonicate three times with a power of 400 watts under ice bath conditions, each time for 30 seconds, with an interval of 10 seconds to make an emulsion (Ningbo Xinzhi Cell Ultrasonic Breaker), and place the emulsion on a magnetic stirrer After the organic phase was completely evaporated to dryness, an aqueous solution of nanoparticles was formed. After the nanoparticles are ultrafiltered to remove unencapsulated drugs, they are lyophilized into powders for long-term storage.

[0056] from figure 1 It can be seen that the nanop...

Embodiment 2

[0057] Example 2: Characterization of Nanoparticles

[0058] Dissolve 1mg of nanoparticles in 1ml of water, and measure the potential particle size as shown in Table 1. figure 2 As shown, it can be found that the size of the nanoparticles prepared by the present invention is about 100 nanometers, which is suitable as a drug carrier.

[0059] Table 1 Size potential of PCL nanoparticles modified by different surfactants

[0060]

[0061] The potential is negative, and the particle size distribution of nanoparticles before and after freeze-drying is analyzed as follows: image 3 , Figure 4 As shown, the particle size of PCL / L61 / F68 nanoparticles changed little before and after freeze-drying, while the particle size of PCL / L61 nanoparticles was above 1 micron after freeze-drying. This shows that without the protection of F68, the lyophilization process will cause the aggregation of nanoparticles to be unstable.

Embodiment 3

[0062] Example 3: Investigating the ability of Pluronic L61 to inhibit the efflux of drug-resistant cells

[0063] The drug-resistant ability exhibited by drug-resistant cells is mainly the efflux ability of P-gp. Drug resistance develops by efflux of chemotherapeutic drugs outside the cell. Rho123 is a classic substrate of P-gp, and the drug resistance of cells can be evaluated by measuring the concentration of Rho123 in cells.

[0064] Digest A549T cells (Nanjing Kaiji Biological Co., Ltd.), according to 5 × 10 5 pc / ml into EP tubes, 1ml per tube. 10, 20, 50, and 100 μg of Pluronic L61 were added respectively, and 5 μM rhodamine 123 (Rho123) (Sigmaaldrich Company, USA) was added and incubated for 1 hour. Centrifuge to remove the supernatant, and add PBS to resuspend and wash for three times. Add 300 μl of cell lysate (Shanghai Sangon Bioengineering Co., Ltd.), and take 100 μl to a bioluminescence detector (Promega, USA) to determine the fluorescence reading. The protein...

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Abstract

The invention relates to the technical field of medicines, provides a nano-scale delivery system loading two surfactants and having anti-tumor-drug-resistance, and further provides a preparation method of the nano-scale delivery system and application of the nano-scale delivery system in preparation of anti-tumor medicines. Two surfactants loaded in the drug-loaded nano-particles are Pluronic L61 and Pluronic F68, wherein Pluronic L61 has excellent anti-drug-resistance and excellent biocompatibility, has the activity independent of types of chemotherapeutic drugs and tumors and can be widely applied to chemosensitization of multiple tumors and Pluronic F68 has excellent water solubility and safety, is capable of remarkably improving stability of nano-particles in water and guaranteeing in-vivo long circulation of the nano-particles to reach tumor tissues and further has an effect of freeze-drying protection and no extra freeze-drying protective additive needs to be added.

Description

[0001] Technical field: [0002] The invention relates to the technical field of medicine, in particular to an anti-tumor and drug-resistant nano-delivery system loaded with two surfactants and a preparation method thereof. [0003] Background technique: [0004] Chemotherapy of tumors has always been the most powerful and most commonly used means of tumor treatment, but the phenomenon of multi-drug resistance produced in the course of treatment is the main factor causing failure. Multidrug resistance (MDR) refers to the occurrence of cross-resistance and broad-spectrum drug resistance to other anti-tumor drugs that are completely different in chemical structure and mechanism of action when tumor cells are resistant to one anti-tumor drug. Phenomenon. MDR is one of the main reasons for the failure of tumor chemotherapy, and it has been involved in a variety of anti-tumor drugs commonly used in clinical practice, such as anthracycline anti-tumor antibiotics (doxorubicin, daunor...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/19A61K9/107A61K31/337A61K47/34A61P35/00
Inventor 高申王晓宇张玮高静台宗光姚翀高原张丽娟胡楚玲顾芬芬
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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