Method for preparing shell-sheddable polymer micelle drug carrier

A technology of polymer glue and hydrophilic polymer, which is applied in the field of preparation of polymer micellar drug carriers, and can solve the problems of few research reports

Inactive Publication Date: 2012-04-04
TONGJI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, the research work in this field has just starte...

Method used

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  • Method for preparing shell-sheddable polymer micelle drug carrier
  • Method for preparing shell-sheddable polymer micelle drug carrier
  • Method for preparing shell-sheddable polymer micelle drug carrier

Examples

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Embodiment 1

[0028] The invention provides a novel PEG shell bridged by disulfide bonds, which can be shed and loaded with tumor drugs. It is characterized in that under the condition of glutathione reduction in tumor cells, the disulfide bond is broken, and the drug can be released rapidly to achieve the controlled release of the drug to the tumor cells, forming a new type of high-efficiency tumor drug carrier.

[0029] Aminated methoxypolyethylene glycol (mPEG-SS-NH 2 ) is a hydrophilic polymer, β-benzyloxycarbonyl protected polylysine (PzLL) is a hydrophobic polymer, and doxorubicin (DOX) is used as a tumor drug model, and the preparation, function and effect of the drug carrier of the present invention are made. Comprehensive and detailed introduction:

[0030] (1) Acyl chloride of dithiodipropionic acid: Under nitrogen protection, take dithiodipropionic acid (DTDP), 1.05g, 5mmol and dissolve it in 5mL thionyl chloride (SOCl 2 ) solution, reacted at 85°C for 4h, then spin-dried SOCl ...

Embodiment 2

[0036] Preparation of shell exfoliated polymer micelles and determination of the lowest critical micelle concentration

[0037] Amphiphilic polymer micelles were prepared according to the method of Example 1, and then the micelles were prepared and the minimum critical micelle concentration (CMC) was determined.

[0038] The mPEG-SS-PzLL polymer micelles are obtained by dialysis, and the particle size is measured by dynamic light scattering (DLS). The particle size is about 302nm, the particle size distribution is narrow, and the PDI is 0.048±0.005, such as figure 1 As shown, the micelles are in a spherical shape, and the electron microscope pictures are as follows figure 2 shown.

[0039] The minimum critical micelle concentration (CMC) of the micelles was determined by encapsulating the hydrophobic probe fluorescent pyrene. To ten 10mL centrifuge tubes, add 1mL concentration of 6×10 -6 The acetone solution of mol / L pyrene was placed in a centrifuge tube, and after the ac...

Embodiment 3

[0041] Glutathione stimulation-induced shedding of micellar shell

[0042] The amphiphilic polymer micelles were prepared according to the method in Example 2, and then the micelles shell exfoliation induced by glutathione (GSH) stimulation was studied.

[0043] Micellar shell shedding properties were illustrated by measuring the change in particle size of polymeric micelles using DLS in a 10 mM GSH environment. After adding 10mM GSH for 2h, the particle size of the polymer increased from 300nm to 419nm, and the PDI increased from 0.048 to 0.22, from Figure 5 shown. When the time was increased to 4h, a large aggregation occurred, which was due to the breaking of the disulfide bond, which caused the departure of the hydrophilic PEG, resulting in the aggregation of the hydrophobic end. Thus it is proved that under the environment of glutathione, the micellar shell layer can be shed and the drug can be released.

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Abstract

The invention relates to a method for preparing a shell-sheddable polymer micelle drug carrier. The drug carrier is a disulfide bond bridging amphiphilic copolymer, and the disulfide bond can be rapidly cracked under reduction environment in cells to realize the intelligent drug release function through the shell shedding, so the amphiphilic copolymer can rapidly self-assemble into micelle nanoparticles and loading drugs in water. Compared with drug carriers prepared with the prior art, the shell-sheddable polymer micelle drug carrier allows the drug release rate under high concentration glutathione environment to be 3-5 times faster than the drug release rate under glutathione-free environment, can be used to control the release of drugs in tumor cells, and has obvious inhibition on the tumor cells, and the drug carrying micelle particles can stably clad anticancer drugs, so a novel high efficiency drug carrier system is provided for the tumor treatment.

Description

technical field [0001] The invention relates to a drug carrier for intelligent release of drugs in cells, in particular to a preparation method of a polymer micelle drug carrier whose shell layer can be shed. Background technique [0002] In the past two decades, research on polymer nanomicelle carriers such as micelles, vesicles, capsules, and nanotubes has gradually deepened. At present, there are at least three polymer nanomicelle drug carriers (SP1049C, NK911 and Genexol -PM) has been approved for clinical use, which has greatly promoted the development of nanomedicine. However, polymer nanomicelles also face some shortcomings as drug carriers. Chemotherapy drugs generally need to enter the tumor cells to produce curative effect. However, the drug release behavior of traditional nanocarriers has no obvious difference between the inside and outside of the cells. Most of the drugs are released outside the cells, resulting in low bioavailability of drugs and side effects. ...

Claims

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Application Information

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IPC IPC(8): A61K9/00A61K47/34A61K47/36A61K47/38A61K31/337A61K31/4745A61K31/704A61P35/00
Inventor 李永勇温惠云董海青徐梦
Owner TONGJI UNIV
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