Targeting polymer micelle containing acid-sensitive subsurface, and preparation method thereof

A polymer glue and polymer technology, applied in the fields of pharmacy, biomedical engineering, and chemistry, can solve the problems that fluorescent organic dye molecules are prone to photobleaching and cannot effectively overcome the masking, and achieve the effect of real-time monitoring of fluorescence imaging

Inactive Publication Date: 2012-05-09
SUN YAT SEN UNIV
View PDF3 Cites 12 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are two major difficulties in the development and research of fluorescence imaging technology and fluorescent probes: one is that the autofluorescence of cells in the visible light region cannot effectively cover

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
  • Targeting polymer micelle containing acid-sensitive subsurface, and preparation method thereof
  • Targeting polymer micelle containing acid-sensitive subsurface, and preparation method thereof
  • Targeting polymer micelle containing acid-sensitive subsurface, and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0026] Example 1

[0027] Synthesis of Folic Acid Modified Triblock Copolymer FA-PEG-P(Asp-dip)-CA with Acid Sensitive Middle Segment

[0028] (1) Synthesis of Polyethylene Glycol (Allyl-PEG-OH) with an allyl group at one end and a hydroxyl group at the other end

[0029] Mix the tetrahydrofuran solution of potassium naphthyl (4 mL) with allyl alcohol (0.75 mL) and stir for 15 minutes in a dry reaction flask. Then under the protection of argon, add anhydrous tetrahydrofuran (20 mL) and 18-crown-6 in tetrahydrofuran (containing 1.5 g 18-crown-6 and 5 mL anhydrous tetrahydrofuran), stir for 15 minutes and place the mixture in Cool in an ice-salt bath and slowly pass in dry ethylene oxide, maintain the low temperature for 24 hours to continue the polymerization reaction, and continue the reaction for 72 hours at room temperature.

[0030] (2) Polyethylene glycol with an allyl group at one end and an amino group at the other end (Allyl-PEG-NH 2 )Synthesis

[0031] Weigh Allyl-PEG-OH (Mn=...

Example Embodiment

[0045] Example 2

[0046] Preparation of targeted polymer micelles with acid-sensitive subsurface layer

[0047] (1) Preparation of samples loaded with QD micelles: The mixture of FA-PEG-P(Asp-dip)-CA (2.0 mg) and PEG-P(Asp-dip)-CA (8.0 mg) was dissolved in tetrahydrofuran (THF, 1.0 mL), add dropwise to PBS (10 mL, pH=5.0) under ultrasonic conditions, stir overnight to evaporate the THF naturally, filter with a 0.22 μm filter membrane, and add the negative electron point CdSe / ZnS (100 μL, 8 μmoL / L), mix well and stand still for 30 minutes, adjust the pH to 7.4, and centrifuge at 6000r / min to remove unloaded quantum dots.

[0048] (2) Preparation of micelles loaded with QD and paclitaxel: the mixture of FA-PEG-P(Asp-dip)-CA (2.0 mg) and PEG-P(Asp-dip)-CA (8.0 mg) and PTX (1.0 mg) dissolved in tetrahydrofuran (THF, 1.0 mL), added dropwise to PBS (10 mL, pH=5.0) under ultrasound, stirred overnight to evaporate THF naturally, and filter the PTX with a 0.45 μm filter membrane Remove t...

Example Embodiment

[0052] Example 4

[0053] In vitro drug release test of targeted polymer micelles with acid-sensitive subsurface layer (taking paclitaxel-loaded micelles as an example)

[0054] Use dialysis to do the in vitro release test of paclitaxel. The newly made paclitaxel-loaded PEG-P(Asp-dip)-CA micelles were divided into two parts, one part maintained its pH value at 5.0, and the other part was adjusted to 7.4. Then divide each pH sample into three parts (parallel experiment) and put it into a dialysis bag with a molecular weight cut-off of 14000 Da. Put the dialysis bag into 100 mL of PBS buffer with the same pH value. Placed 37 ℃ In the shaker, at a rotation speed of 75 r / min, take samples at a set time point, and then add the same volume of fresh buffer. Detect the concentration of the sample by HPLC and calculate the cumulative release at different time points. The chromatographic column model used by HPLC is Ultimate from welch materials company ? AQ-C18, 5 μm, 4.6×250mm, mobile...

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
Diameteraaaaaaaaaa
Apertureaaaaaaaaaa
Login to view more

Abstract

The invention relates to a targeting polymer micelle containing acid-sensitive subsurface, and a preparation method thereof. The polymer micelle is in a core-shell structure. Targeting ligand molecules are grafted on a hydrophilic segment terminal of the shell, and a hydrophobic anti-tumor medicine is loaded by a hydrophobic segment of the core. An acid-sensitive response subsurface exists between the core and the shell, wherein the acid-sensitive response subsurface can load negative electricity quantum dots. When a pH value is 5.0, the acid-sensitive layer is hydrophobic; when the pH value is 7.4, the acid-sensitive layer is hydrophobic. According to the invention, with the targeting molecules, the tumor targeting function of the micelle is realized; with the quantum dots loaded on the acid-sensitive subsurface, a visualizing function is realized; with low-pH-responsibility of the acid-sensitive subsurface, a controlled-release function can be realized, and the release of the medicine can be controlled. With the micelle system provided by the invention, the release behavior of the medicine is improved, and a premature-release problem of the micelle system in blood circulation ispossible to be solved. With an internalization behavior mediated by the targeting molecules, the treatment effect of the medicine is enhanced. With the loaded quantum dots, monitoring during the treatment process can be realized.

Description

[0001] technical field [0002] The invention relates to the fields of chemistry, pharmacy and biomedical engineering, in particular to the preparation of a targeting polymer micelle with an acid-sensitive subsurface layer and its application in drug controlled release and imaging. Background technique [0003] Tumors are a serious threat to human health, and the mortality rate remains high. There are three main approaches to cancer treatment: surgery, radiation therapy, and chemotherapeutic drugs (chemotherapy). The first two are localized treatments, and chemotherapy is usually given when the tumor has spread and metastasized. Most of the chemotherapeutic drugs commonly used in clinic are hydrophobic drugs, and their solubility in water is very low, which limits their application. In clinical use, small molecule surfactants are often used to emulsify and solubilize hydrophobic chemotherapy drugs, but the blood stability of this dosage form is very poor, the added excipien...

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
IPC IPC(8): A61K9/14A61K47/34A61K45/00A61K49/00A61P35/00A61K47/22
Inventor 帅心涛王伟伟程度巩发明
Owner SUN YAT SEN 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