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TA-Fe (III) modified PLGA nanoparticles coating doxorubicin hydrochloride and preparation method thereof

A technology of doxorubicin hydrochloride and nano-particles is applied in the field of medicine to achieve the effects of prolonging the action time of the medicine, realizing long-acting sustained release, and the preparation method being simple and quick.

Pending Publication Date: 2019-09-17
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, TA-Fe(III) complexes have not been well studied as a surface modification of PLGA NPs to control drug release.

Method used

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  • TA-Fe (III) modified PLGA nanoparticles coating doxorubicin hydrochloride and preparation method thereof
  • TA-Fe (III) modified PLGA nanoparticles coating doxorubicin hydrochloride and preparation method thereof
  • TA-Fe (III) modified PLGA nanoparticles coating doxorubicin hydrochloride and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1. Preparation of DOX-loaded TA-PLGA NPs

[0043] Reagents: monomethoxypolyethylene glycol poly(lactic-co-glycolic acid) mPEG5000-PLGA50 / 5028000 was purchased from Jinan Daigang Biological Engineering Co., Ltd., dichloromethane and ethyl acetate were purchased from Shanghai Chemical Reagent Co., Ltd., and adriamycin ( DOX, purity 98%) was purchased from Shanghai McLean Biochemical Co., Ltd., polyvinyl alcohol PVA was purchased from Shanghai Lingfeng Chemical Reagent Co., Ltd., and tannic acid (TA) was purchased from Aladdin Industrial Company. Other biochemical reagents belong to domestic conventional analytical reagents.

[0044] Reagent preparation:

[0045] 1% PVA solution: Weigh 1g of PVA, heat and dissolve with ultrapure water, and dilute to 100mL.

[0046] 10mg / mL TA solution: Weigh 1g TA, dissolve it in ultrapure water, and dilute to 100mL.

[0047] 10mg / mL FeCl 3 ·6H 2 O solution: weigh 1g FeCl 3 ·6H 2 O, dissolved in ultrapure water, and adjusted...

Embodiment 2

[0053] Example 2. Characterization of DOX-loaded TA-PLGA NPs

[0054] Reagent preparation:

[0055] PBS solution: weigh 0.8g NaCl, 0.02g KCl, 0.024g KH 2 PO 4 , 0.144g Na 2 HPO 4 , heated to dissolve with ultra-pure water, set the volume to 100mL, adjusted the pH with NaOH solution or concentrated HCl solution to 8.5, 7.4, 6.5, 6.0, 5.0, 4.0, 3.0, 2.0 and 1.0, respectively.

[0056] Nanoparticles (about 1 mg) were suspended in ultrapure water by sonication before measurement. The average particle size, particle size distribution and Zeta potential of DOX-loaded nanoparticles were measured using a ZetasizerZEN3600 (Malvern Instruments, Malvern, UK). The morphology of the prepared nanoparticles was observed using a transmission electron microscope (TEM). The DOX-loaded nanoparticle suspension was placed on a copper grid with a film, dried for 10 min, and observed by TEM (JEM-1400microscope, JEOL, Japan). In addition, the elemental composition on the surface of TPLGA NPs w...

Embodiment 3

[0061] Example 3. In vitro cellular uptake and cytotoxicity of DOX-loaded TA-PLGA NPs

[0062] Reagents and kits: MTT, penicillin and streptomycin mixed solution, DMSO were purchased from Beijing Suolaibao Company, DMEM medium, fetal bovine serum, trypsin were purchased from Gibco Company (USA), Hoechst 33342 were purchased from Beyotime Institute of Biotechnology . Other biochemical reagents belong to domestic conventional analytical reagents.

[0063] Cell lines and medium: human breast cancer cells MCF-7 and B-Cap-37, culture conditions are 37°C, 5% CO 2 Concentration, the medium is DMEM medium (containing 10% fetal bovine serum).

[0064] Reagent preparation:

[0065] DMEM complete medium: Take 90mL DMEM culture medium (1×), add 10mL fetal bovine serum, 1mL penicillin (100IU / L) and 1mL streptomycin (100mg / L), mix well, and store at 4°C.

[0066] 5mg / mL MTT solution: Weigh 250mg MTT and dissolve it in 50mL PBS, dissolve it fully at 60°C, filter it with a 0.22μm sterile ...

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Abstract

The invention provides TA-Fe (III) modified PLGA nanoparticles coating doxorubicin hydrochloride and a preparation method thereof. The mPEG-PLGA is selected as a carrier material, TA and Fe (III) are used as modification materials, and the nanoparticles are prepared by combination of a multiple emulsion-solvent volatilization method and coordination modification of the TA and Fe (III). The encapsulation efficiency of the nanoparticles is 80.14+ / -9.79%, and the drug loading is 0.85+ / -0.08%. The particle size of the nanoparticles is 146.9+ / -14.3 nm, the Zeta potential is -21.0+ / -0.2 mV, and the polydispersity index is 0.214+ / -0.113. The surfaces of the nanoparticles obtained by the preparation method are smooth and round without adhesion, and the nanoparticles have controllable size, small particle size and narrow range of particle size, are convenient for intravenous injection, and have good sustained release effect. The TA-Fe (III) modified nanoparticles have a good drug encapsulation effect, can significantly reduce drug burst release and have a pH responsiveness effect. Therefore, the nanoparticles have broader application prospects in targeted delivery as an anti-tumor drug.

Description

technical field [0001] The present invention relates to the technical field of medicine, more specifically, relate to the TA-Fe(III) modified monomethoxypolyethylene glycol polylactic-co-glycolic acid copolymer (mPEG-PLGA) nanoparticle that packs doxorubicin hydrochloride Preparation and its use as tumor therapy drug. Background technique [0002] Breast cancer is the leading cause of cancer death in women worldwide. So far, in addition to surgery, breast cancer is mainly treated clinically through chemotherapy. However, most anticancer drugs have high toxicity and low specificity, leading to systemic toxicity and severe side effects. Polymeric nanoparticles (PNPs) have been used as promising carriers of anticancer drugs as sustained, controlled and targeted drug delivery systems, improving therapeutic efficacy and reducing side effects on normal organs. [0003] Poly(D,L-lactide-co-glycolide) (PLGA) is a synthetic polymer commonly used in biological applications, approve...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/54A61K31/704A61P35/00
CPCA61K31/704A61K47/6937A61K47/547A61P35/00
Inventor 马兴元胡发彪郑文云郑玉林刘海鹏
Owner EAST CHINA UNIV OF SCI & TECH
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