Method for preparing docetaxel and sulforaphane loaded self-assembled nano-particle and application of nano-particle

A self-assembled nanoparticle and sulforaphane technology, applied in the field of medicine, can solve the problems of tumor volume reduction, no breast cancer treatment, and difficult to eradicate breast cancer recurrence, etc., and achieve the effect of broad application prospects

Inactive Publication Date: 2014-06-25
SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

(2) Postoperative adjuvant endocrine therapy, prolongation of estrogen exposure time in breast cancer tissue will increase the risk of breast cancer, based on this background reason, it is possible to reduce or cut off the source of estrogen, or try to resist the effect of estrogen Prevents estrogen from stimulating breast cancer cells and inhibits breast cancer growth
[0003] Although the above combined therapy has made great progress compared with single surgery, radiotherapy, and chemotherapy, these methods still face some problems: (1) Although the dose of adjuvant chemotherapy and endocrine therapy is reduced, it also alleviates the damage to normal tissue
(2) Although molecular targeted drug delivery has improved targeting, this effect is often aimed at a single link in the pathological process of breast cancer, which has great individual differences for different patients
(3) There is a common problem in the current treatment methods: the first-line drugs used in the treatment of breast cancer in these treatments are all aimed at differentiated tumor cells, which can kill such cells in a short period of time and reduce the tumor volume Even disappear, but it is difficult to eradicate the recurrence of breast cancer, and there is no treatment for breast cancer from the root cause
[0007] So far, no literature has reported self-assembled nanoparticles of hyaluronic acid-modified poly(lactic-co-glycolic acid) loaded with docetaxel and sulforaphane

Method used

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  • Method for preparing docetaxel and sulforaphane loaded self-assembled nano-particle and application of nano-particle
  • Method for preparing docetaxel and sulforaphane loaded self-assembled nano-particle and application of nano-particle
  • Method for preparing docetaxel and sulforaphane loaded self-assembled nano-particle and application of nano-particle

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Experimental program
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Embodiment 1

[0083] Embodiment 1: the synthesis of PLGA-b-HA block copolymer

[0084]In reference "Jeong YI, Kim do H, Chung CW, Yoo JJ, Choi KH, Kim CH, et al. Self-assembled nanoparticles of hyaluronic acid / poly(DL-lactide-co-glycolide) block copolymer. Colloids Surf B Based on Biointerfaces2012;90:28-35", polylactic acid-glycolic acid copolymer PLGA and hyaluronic acid (HA) were first connected to form a block copolymer by reductive amination method.

[0085] PLGA model RG502H and HA molecular weight 5600Da were selected as the hydrophobic and hydrophilic ends of the carrier. The specific preparation method is three steps, such as figure 1 Shown:

[0086] (1) Preparation of terminally aminated HA, accurately weigh 1.0g of HA and dissolve in 30.0ml of acetic acid / sodium acetate (pH=5.6, 2%w / w) buffer solution, add 1.0ml after HA is completely dissolved ml of 1,4-butanediamine. Stir magnetically at 50°C for 24 hours to form an imine, then add 0.2g of sodium cyanoborohydride, then adju...

Embodiment 2

[0089] Embodiment 2: the preparation of the PLGA-b-HA nanoparticle loaded with docetaxel and sulforaphane

[0090] The present invention is based on solvent dialysis (see: Shahin M, Lavasanifar A.Novel self-associating poly(ethylene oxide)-bpoly(epsilon-caprolactone) based drug conjugates and nano-containers for paclitaxel delivery. Int J Pharm2010;389:213e22. ) was modified accordingly to prepare drug-loaded PLGA-b-HA nanoparticles. The solvent dialysis method is to directly dissolve the drug and polymer material in a water-soluble organic solvent, and then dialyze in deionized water or buffer salt to remove the organic solvent to obtain drug-loaded nanoparticles. Our modified method is: after dissolving the drug and polymer Slowly add deionized water to the organic phase of the drug material and stir to form drug-loaded nanoparticles, and then dialyze to remove the organic solvent. The purpose of this improvement is to increase the drug loading capacity of the drug ( figu...

Embodiment 3

[0094] Embodiment 3: the half maximal inhibitory concentration (IC) of drug-loaded nanoparticles to breast cancer and breast cancer stem cells 50 )

[0095] The present invention uses the MTT method (see Tim Mosmann, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, Journal of Immunological Methods, 1983, 65(1-2):55-6,3) to evaluate drug loading In vitro cytotoxicity, i.e., IC, of ​​nanoparticles against breast cancer and breast cancer stem cells 50 value. The evaluation of in vitro toxicity of breast cancer cells (MCF-7) and breast cancer stem cells (selected by suspension culture) is now described separately.

[0096] 1. Toxicity evaluation on breast cancer:

[0097] (1) MCF-7 cells in the logarithmic growth phase were digested with trypsin to make a single cell suspension, and the cell density was adjusted to 5×10 4 Cells / mL, inoculated in 96-well plate at a density of 5000 cells / well, that is, adding 0.1ml ...

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Abstract

The invention relates to the technical field of medicines, and provides a docetaxel and sulforaphane loaded hyaluronic acid modified poly(lactic-co-glycolic acid) copolymer self-assembled nano-particle, a preparation method thereof and an application of the self-assembled nano-particle in preparing a medicine for treating breast cancer. The microscopic structure of the nano-particle comprises a hydrophobic PLGA (poly(lactic-co-glycolic acid)) core and a hydrophilic HA (hyaluronic acid) shell, wherein the PLGA core is used for wrapping a medicine DTX (docetaxel) or SFN (sulforaphane), and the hydrophilic shell HA can target a breast cancer stem cell highly expressing a CD44 receptor. In-vitro cytotoxicity tests indicate that the drug-loaded nano-particle can play a good role in resisting differentiation of mammary gland cells and breast cancer stem cells when compared with free medicines; in-vivo tumor inhibition experiments indicate that the drug-loaded medicine is more effective than free medicines and combined free medicines, and has a small systematic toxicity. The nano-particle can play a role in simultaneously performing target differentiating on mammary gland cells and breast cancer stem cells, and a new strategy is provided to treatment of breast cancer.

Description

technical field [0001] The invention belongs to the field of medical technology, specifically, it relates to the preparation of PLGA-HA self-assembled nanoparticles loaded with docetaxel (DTX) and sulforaphane (SFN), targeting differentiated breast cancer cells and breast cancer stem cells, In order to achieve the purpose of eradicating breast cancer. Background technique [0002] Breast cancer is the most common malignant tumor in women, and the incidence rate in my country is increasing year by year, and the incidence rate tends to be younger. Therefore, the prevention and treatment of breast cancer has become an important task of medical research in our country. At present, the treatment of breast cancer has developed from a single surgical treatment to a comprehensive treatment including surgery, chemotherapy, radiotherapy and biological treatment. These methods are mainly manifested in the following aspects: (1) Postoperative adjuvant chemotherapy, which uses a variet...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K47/36A61K31/337A61P35/00A61K31/26
Inventor 钟延强黄景彬张翮鲁莹王新霞张国庆陈琰俞媛邹豪刘俊杰孙治国陶春贾婷婷吴珊向婧洁
Owner SECOND MILITARY MEDICAL UNIV OF THE PEOPLES LIBERATION ARMY
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