Drug delivery system with tumor microenvironment adjustment and targeting function and application thereof in pharmacy

A tumor microenvironment and delivery system technology, which is used in the screening of active ingredients of traditional Chinese medicine and its preparation field, can solve the problems of poor solubility of natural products, inability to accumulate tumor sites, and short circulation half-life, and achieves short half-life improvement and delivery efficiency. Accumulation and secretion reduction effect

Inactive Publication Date: 2020-03-24
FUDAN UNIV
View PDF1 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, natural products have poor solubility, short circulation half-life in vivo, easy removal, and inability to accumulate in tumor sites. Based on the current state of the art, the inventors of the present application intend to provide tumor microenvironment and targeting functions. Drug delivery system and its application in pharmaceuticals, especially in the treatment of pancreatic tumors

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Drug delivery system with tumor microenvironment adjustment and targeting function and application thereof in pharmacy
  • Drug delivery system with tumor microenvironment adjustment and targeting function and application thereof in pharmacy
  • Drug delivery system with tumor microenvironment adjustment and targeting function and application thereof in pharmacy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1: Preparation and characterization of arketone nano-preparations and their cytotoxicity

[0037] The nano drug delivery system was prepared by emulsified solvent volatilization method. Weighed 5mg of alkalone powder and 250mg of mPEG-PLA, dissolved in 10mL of dichloromethane, added 2mL of 1% sodium cholate, and ultrasonicated with a 220W probe for 2.4min in an ice bath. After an interval of 2 s, disperse with 80 mL of 0.5% sodium cholate solution for 10 min, and remove residual dichloromethane by rotary evaporation at 40°C for 20 min. After rotary evaporation, centrifuge at 15,000 rpm / min for 1 h at 4°C, discard the supernatant to obtain drug-loaded nanoparticles (Frax-NP, free drug is Frax-Free). The particle size of the nanoparticles was measured with a Malvern Particle Size / Zeta Potential Meter. After NIH3T3 cells adhered to the wall for 24 hours, drugs with different concentration gradients were given, and after incubation for 24 hours, the cytotoxicity of...

Embodiment 2

[0039] Example 2: Investigation of alkone on the M2 typing of macrophages and the expression of cellular proteins in CAFs

[0040] In order to verify whether the alkone nanosystem can affect the tumor-associated macrophages in the tumor microenvironment, the changes in the proportion of macrophages of the M2 type after administration were investigated. Unactivated RAW 264.7 cells were used as negative control group, and RAW264.7 activated with 10 ng / ml IL-13 was used as M2 type positive control group. The effect of free drug and nano-preparation containing 20 μM alkone on macrophage M2 type was compared. Inhibitory effect. Specifically, in a 6-well plate of RAW264.7 cells, except for the negative control group, 10 ng / ml of stimulatory factor IL-13 was added to each well, placed in the incubator for 24 hours, and Frax-Free and Frax-NP and an equal volume of phosphate buffered saline (PBS), the cells were collected after 12 hours, stained with a fluorescent dye PE-labeled M2 ma...

Embodiment 3

[0043] Example 3: Research on the mechanism of action of arketone on CAFs

[0044] CAFs have been confirmed to exist in large quantities in the tumor microenvironment, which is a physical barrier for chemotherapy drugs to penetrate into tumor cells, and plays an important role in supporting and promoting tumor growth, drug resistance, and metastasis; in advanced cancer, TGF-β / smad The activation of the pathway can promote the abnormal activation of CAFs and deposit a large amount of extracellular matrix, increase the interstitial hydraulic pressure to squeeze blood vessels, and hinder the delivery of chemotherapy drugs; in this experiment, Western Blot was used to investigate the TGF-β / smad in CAFs cells after administration of dithone. For the expression of pathway-related proteins, NIH3T3 stimulated with 10ng / ml TGF-β for 24h was used as a positive control, and the free drug and nano-preparation containing 20μM arketone were administered for 2h, 8h, and 24h respectively to in...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
molecular weightaaaaaaaaaa
Login to view more

Abstract

The invention belongs to the field of screening of effective components of traditional Chinese medicines and preparations of the effective components, and relates to a drug delivery system with tumormicroenvironment adjustment and a targeting function and application thereof in pharmacy, in particular to application in pancreatic tumor treatment. The invention discloses a nano delivery system. Nanoparticles which are constructed from a medical polymer polylactic acid material, have good biocompatibility and biodegradability and have the effects of regulating a tumor microenvironment and increasing blood perfusion are adopted, a section of functional polypeptide CGKRK is covalently bonded to the surface, the CGKRK can target heparan sulfate which is highly-expressed in the tumor microenvironment, and the tumor targeting property is improved; and natural drug monomers are physically entrapped in hydrophobic cores of the nanoparticles through an emulsifying solvent evaporation method, sothat the solubility of the drug is improved, and the in-vivo circulation time of the drug is prolonged. The established drug-loaded nano system can inhibit the excessive activation of CAFs, reduce the proportion of M2 macrophages, effectively improve the tumor microenvironment and increase the accumulation of the drug at the tumor site.

Description

technical field [0001] The invention belongs to the field of screening and preparation of active ingredients of traditional Chinese medicine, and relates to a drug delivery system with functions of regulating tumor microenvironment and targeting and its application in pharmacy, especially in the treatment of pancreatic tumors. The present invention involves encapsulating hydrophobic natural drug monomers with a short half-life in biodegradable polylactic acid nanoparticles for targeted delivery to tumor sites to improve the tumor microenvironment and increase the penetration and accumulation of subsequent chemotherapy drugs in tumor sites , and its mechanism of action was investigated. Background technique [0002] The prior art discloses that pancreatic cancer is a malignant digestive tract cancer, and the resistance to treatment is mainly related to the immunosuppressive tumor microenvironment (TME). Studies have shown that more than 80% of the tumor microenvironment is me...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K47/42A61K47/10A61K31/7068A61K31/365A61P35/00
CPCA61K9/5146A61K9/5153A61K9/5169A61K31/365A61K31/7068A61P35/00A61K2300/00
Inventor 陈钧裴圆圆
Owner FUDAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap