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Polymer nano-micelle entrapped with two drugs and preparation method and application of polymer nano-micelle

A nano-micelle and polymer technology, applied in the field of biomedicine, can solve the problems of cumbersome design and preparation of micelles, difficult realization of chemotherapy drugs, and increased difficulty of research, etc., to achieve excellent clinical application prospects, controllable drug release behavior, Inhibition of tumor growth and metastasis

Pending Publication Date: 2022-07-29
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although a variety of drug-loading systems such as micelles, lipids, and inorganic nanoparticles have been designed to carry a variety of drugs in recent years, it is still difficult to carry chemotherapy drugs with different solubility characteristics, and due to the different characteristics of drugs, The design and preparation of micelles are often tedious and complicated, which increases the difficulty of research

Method used

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  • Polymer nano-micelle entrapped with two drugs and preparation method and application of polymer nano-micelle
  • Polymer nano-micelle entrapped with two drugs and preparation method and application of polymer nano-micelle
  • Polymer nano-micelle entrapped with two drugs and preparation method and application of polymer nano-micelle

Examples

Experimental program
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Effect test

Embodiment 1

[0070] Example 1. Preparation of polymer nanomicelles that simultaneously encapsulate two drugs according to the present invention

[0071] The mPEG-PCL polymer nanomicelles (Dox-Cur-M) loaded with doxorubicin and curcumin simultaneously were obtained in two steps.

[0072] Step 1: Preparation of curcumin-encapsulated mPEG-PCL micelles (Cur-M) by solid dispersion method: Curcumin and mPEG-PCL polymer were weighed and added to 5 mL of ethanol to dissolve completely. Then use a rotary evaporator to remove ethanol by rotary evaporation for 10 minutes at 60°C, rotating speed of 100rpm / min and negative pressure. After forming a transparent film, add distilled water and place it in a water bath for hydration at 60°C to obtain Cur-M micelle solution. , the curcumin concentration in the solution is 1.5mg / mL, and the mPEG-PCL polymer concentration is 60mg / mL

[0073] Step 2: Encapsulation of doxorubicin into Cur-M micelles by pH-induced self-assembly. First, 0.1 mL of PBS (10×, pH 7....

experiment example 1

[0079] Experimental Example 1. Characterization of physicochemical properties of Dox-Cur-M micelles of the present invention

[0080] 1. Experimental method

[0081] 1.1 Determination of particle size of Dox-Cur-M micelles

[0082] All Dox-Cur-M micelles tested below are Dox-Cur-M micelles prepared in Example 1.

[0083] The hydrated particle size and distribution of Dox-Cur-M micelles were measured by dynamic light scattering (DLS) using a laser scattering particle sizer (Nano-ZS, Malvern Instrument, UK); the samples were tested at 25°C and the test was repeated 3 times, take the average value.

[0084] 1.2 Morphology of real Dox-Cur-M micelles observed by transmission electron microscopy

[0085] The morphology of Dox-Cur-M micelles was observed using transmission electron microscopy (TEM). Before observation, a drop of diluted Dox-Cur-M micelles of Example 1 was dropped onto a copper mesh, then negatively stained with phosphotungstic acid solution, dried and placed unde...

experiment example 2

[0093] Experimental example 2. Establishment of HPLC analysis method and determination of encapsulation efficiency and drug loading

[0094] 1. Experimental method

[0095] 1.1 Chromatographic conditions

[0096] Waters Alliance 2695 high performance liquid chromatograph, chromatographic column Inertsil / WondaSil C18 (4.6x250mm, 5um), column temperature 30°C, injection volume 20μL, flow rate: 1.0mL / min, the mobile phase for curcumin detection is acetonitrile: 1% acetic acid solution (60 / 40, V / V), detection wavelength 420nm; mobile phase for doxorubicin detection is methanol: acetonitrile: 1% acetic acid solution (40 / 10 / 50, V / V), detection wavelength 252nm.

[0097] 1.2 Standard curves of curcumin and doxorubicin

[0098] Precisely weigh 10 mg of curcumin using an electronic scale, place it in a 100 mL volumetric flask, and add 100 mL of methanol to dissolve it to obtain a stock solution. The methanol standard solutions of curcumin with different concentrations of 0.1, 0.4, 0...

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Abstract

The invention provides a polymer nano-micelle entrapped with two drugs as well as a preparation method and application of the polymer nano-micelle. The polymer nano-micelle is prepared from a methoxy polyethylene glycol-polycaprolactone block copolymer mPEG-PCL, curcumin and adriamycin, the micelle is non-toxic, small in particle size, stable, high in encapsulation efficiency and controllable in drug release behavior, compared with a micelle entrapped with a single drug, the toxicity and apoptosis promoting effect on 4T1 breast cancer cells are obviously enhanced, and the drug release behavior is controllable. Tumor growth and metastasis can be effectively inhibited, and tumor angiogenesis is inhibited. According to the invention, the biodegradable methoxy polyethylene glycol-polycaprolactone (mPEG-PCL) polymer nano-micelle is used for simultaneously entrapping adriamycin and curcumin, the preparation process is simple, no surfactant or additive is used in the preparation process, the safety in clinical application is ensured, and the nano-micelle has an excellent clinical application prospect.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a polymer nanomicelle encapsulating two kinds of medicines and a preparation method and application thereof. Background technique [0002] Cancer remains a public health concern worldwide, with cancer being the second leading cause of death in the United States and is expected to surpass cardiovascular disease as the leading cause of death in the next few years. Among them, breast cancer is the leading cause of cancer death in women aged 20-59, and new cases of breast cancer will account for 29% of all new cancer cases in 2015. Chemotherapy, as a routine means of breast cancer treatment, can reduce the risk of tumor recurrence and metastasis, and improve the overall survival rate of patients. It is an indispensable part of comprehensive breast cancer treatment. However, most chemotherapeutic drugs are cytotoxic drugs, which can damage the normal tissues of the body while k...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/34A61K31/704A61K31/12A61P35/00
CPCA61K9/1075A61K47/34A61K31/704A61K31/12A61P35/00A61K2300/00
Inventor 孙璐
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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