CN112461716A - 大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法 - Google Patents
大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法 Download PDFInfo
- Publication number
- CN112461716A CN112461716A CN202011199694.8A CN202011199694A CN112461716A CN 112461716 A CN112461716 A CN 112461716A CN 202011199694 A CN202011199694 A CN 202011199694A CN 112461716 A CN112461716 A CN 112461716A
- Authority
- CN
- China
- Prior art keywords
- sorafenib
- emodin
- solution
- standard
- hepg2
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000005511 L01XE05 - Sorafenib Substances 0.000 title claims abstract description 113
- 229960003787 sorafenib Drugs 0.000 title claims abstract description 113
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 title claims abstract description 109
- RHMXXJGYXNZAPX-UHFFFAOYSA-N emodin Chemical compound C1=C(O)C=C2C(=O)C3=CC(C)=CC(O)=C3C(=O)C2=C1O RHMXXJGYXNZAPX-UHFFFAOYSA-N 0.000 title claims abstract description 88
- VWDXGKUTGQJJHJ-UHFFFAOYSA-N Catenarin Natural products C1=C(O)C=C2C(=O)C3=C(O)C(C)=CC(O)=C3C(=O)C2=C1O VWDXGKUTGQJJHJ-UHFFFAOYSA-N 0.000 title claims abstract description 86
- 239000010282 Emodin Substances 0.000 title claims abstract description 86
- RBLJKYCRSCQLRP-UHFFFAOYSA-N Emodin-dianthron Natural products O=C1C2=CC(C)=CC(O)=C2C(=O)C2=C1CC(=O)C=C2O RBLJKYCRSCQLRP-UHFFFAOYSA-N 0.000 title claims abstract description 86
- YOOXNSPYGCZLAX-UHFFFAOYSA-N Helminthosporin Natural products C1=CC(O)=C2C(=O)C3=CC(C)=CC(O)=C3C(=O)C2=C1O YOOXNSPYGCZLAX-UHFFFAOYSA-N 0.000 title claims abstract description 86
- NTGIIKCGBNGQAR-UHFFFAOYSA-N Rheoemodin Natural products C1=C(O)C=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1O NTGIIKCGBNGQAR-UHFFFAOYSA-N 0.000 title claims abstract description 86
- VASFLQKDXBAWEL-UHFFFAOYSA-N emodin Natural products OC1=C(OC2=C(C=CC(=C2C1=O)O)O)C1=CC=C(C=C1)O VASFLQKDXBAWEL-UHFFFAOYSA-N 0.000 title claims abstract description 86
- PKUBGLYEOAJPEG-UHFFFAOYSA-N physcion Natural products C1=C(C)C=C2C(=O)C3=CC(C)=CC(O)=C3C(=O)C2=C1O PKUBGLYEOAJPEG-UHFFFAOYSA-N 0.000 title claims abstract description 86
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 238000000034 method Methods 0.000 title claims abstract description 27
- 230000005764 inhibitory process Effects 0.000 title claims abstract description 16
- 230000035755 proliferation Effects 0.000 title claims abstract description 16
- 238000012795 verification Methods 0.000 title description 2
- 239000000243 solution Substances 0.000 claims abstract description 108
- 239000003814 drug Substances 0.000 claims abstract description 66
- 229940079593 drug Drugs 0.000 claims abstract description 55
- 239000002105 nanoparticle Substances 0.000 claims abstract description 37
- 239000012086 standard solution Substances 0.000 claims abstract description 32
- 238000002835 absorbance Methods 0.000 claims abstract description 18
- 230000000694 effects Effects 0.000 claims abstract description 16
- 238000011068 loading method Methods 0.000 claims abstract description 16
- 238000005538 encapsulation Methods 0.000 claims abstract description 13
- 239000002245 particle Substances 0.000 claims abstract description 10
- 238000012417 linear regression Methods 0.000 claims abstract description 9
- 238000001514 detection method Methods 0.000 claims abstract description 7
- 230000004663 cell proliferation Effects 0.000 claims abstract description 4
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 4
- 238000011835 investigation Methods 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 60
- 238000005303 weighing Methods 0.000 claims description 13
- 239000012876 carrier material Substances 0.000 claims description 12
- 239000000523 sample Substances 0.000 claims description 11
- 239000011550 stock solution Substances 0.000 claims description 9
- 230000004083 survival effect Effects 0.000 claims description 9
- 238000007865 diluting Methods 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 6
- FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 238000002390 rotary evaporation Methods 0.000 claims description 5
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 5
- 239000012498 ultrapure water Substances 0.000 claims description 5
- 238000004364 calculation method Methods 0.000 claims description 4
- 238000002604 ultrasonography Methods 0.000 claims description 4
- 230000003833 cell viability Effects 0.000 claims description 3
- 210000004027 cell Anatomy 0.000 description 17
- 238000001727 in vivo Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 238000009210 therapy by ultrasound Methods 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 5
- 238000002626 targeted therapy Methods 0.000 description 5
- 241000036848 Porzana carolina Species 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 201000007270 liver cancer Diseases 0.000 description 4
- 208000014018 liver neoplasm Diseases 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 206010059866 Drug resistance Diseases 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 108010019160 Pancreatin Proteins 0.000 description 2
- 238000011111 UV-scan method Methods 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000005429 filling process Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000006070 nanosuspension Substances 0.000 description 2
- 229940055695 pancreatin Drugs 0.000 description 2
- 229920000382 poly(ethylene glycol) methyl ether-block-poly(L-lactide-co-glycolide) Polymers 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 206010061623 Adverse drug reaction Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 210000003771 C cell Anatomy 0.000 description 1
- 235000015655 Crocus sativus Nutrition 0.000 description 1
- 244000124209 Crocus sativus Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- SCJNCDSAIRBRIA-DOFZRALJSA-N arachidonyl-2'-chloroethylamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCCl SCJNCDSAIRBRIA-DOFZRALJSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940126523 co-drug Drugs 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 235000013974 saffron Nutrition 0.000 description 1
- 239000004248 saffron Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/02—Investigating particle size or size distribution
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2503/00—Use of cells in diagnostics
- C12N2503/02—Drug screening
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N2015/0038—Investigating nanoparticles
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
- G01N2500/10—Screening for compounds of potential therapeutic value involving cells
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本明公开了一种大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,包括以下步骤:S1、配置标准溶液;S2、对上述标准溶液进行波长扫描;S3、根据扫描确定大黄素的检测波长,测定不同浓度大黄素标准溶液的吸光度值,根据吸光度值对标准溶液进行线性回归,建立标准曲线;S4、对索拉非尼溶液、大黄素联合索拉非尼溶液进行专属性考察;S5、测定不同浓度索拉非尼标准溶液中索拉非尼的含量,建立标准曲线;S6、制备大黄素联合索拉非尼的纳米粒;S7、大黄素联合索拉非尼纳米粒的质量评价,包括外观、粒径、电位、包封率和载药量;S8、考察大黄素联合索拉非尼纳米制剂在抑制HepG2细胞增殖中的作用。
Description
技术领域
本发明涉及医药领域,特别是涉及一种大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法。
背景技术
肝癌是常见的恶性肿瘤,在国内的发病率已呈逐年上升趋势。目前,肝癌的治疗方法除传统的手术治疗外,还有化学治疗、放射治疗及免疫治疗等。各种治疗手段均有自己的优劣势,而化学治疗中的靶向治疗是近年来肿瘤研究的热点。靶向治疗是指通过一定的特异性递药系统将药物分子有针对性的运送至肿瘤组织,当载体到达该组织时,药物集中的释放使肿瘤细胞特异性死亡,却不会累及肿瘤周围的正常组织的一种治疗方法。靶向治疗在临床应用上区别于传统的化学治疗主要价值体现在其能极大地降低宿主的毒副作用,起到增效减毒的作用。近年来,随着靶向治疗研究的不断深入,研究者发现使用单纯小分子靶向药物仍然存在长期使用后肿瘤细胞仍会产生肿瘤多药耐药现象。因此通过将小分子靶向药物与中药提取物联合使用,来达到减少肿瘤耐药情况,增加化疗药物的敏感性,是新兴的一种药物组合方式。纳米技术因其可将药物定向输送到靶部位以及具有延长药物体内循环的特点被广泛关注,越来越多的研究将纳米技术应用于肿瘤靶向治疗。通过可生物降解高分子材料制成的纳米粒,具有粒径小,比表面积大,毒副作用小,延长体内循环作用时间,并能在体内降解等特点,在保持药效的条件下达到缓释药物的作用,同时可以避免药物的泄露和降解,提高药物的疗效;还能精准靶向递送,使药物达到特定的作用部位后在进行释药,可有效降低药物不良反应。两亲性共聚物纳米粒因其特殊的化学结构,可将脂溶性药物包裹于核内,减少药物的毒副作用;同时亲水性外壳可增加药物的稳定性,延长体内循环作用时间。
发明内容
针对上述问题,本发明提供了一种大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,该药物组合制备的制剂可实现2种非水溶性药物的同时治疗,抑制索拉非尼单药耐药,延长药物体内作用时间,在实现提高肝癌治疗的效果同时降低给药次数,增加治疗的顺应性。
本发明的技术方案是:
一种大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,包括以下步骤;
S1、配置标准溶液,其中标准溶液包括:大黄素溶液、索拉非尼溶液和大黄素混合索拉非尼溶液;
S2、对上述标准溶液进行波长扫描;
S3、根据扫描确定大黄素的检测波长,测定不同浓度大黄素标准溶液的吸光度值,根据吸光度值对标准溶液进行线性回归,建立标准曲线;
S4、对索拉非尼溶液、大黄素联合索拉非尼溶液进行专属性考察;
S5、测定不同浓度索拉非尼标准溶液中索拉非尼的含量,建立标准曲线;
S6、制备大黄素联合索拉非尼的纳米粒;
S7、大黄素联合索拉非尼纳米粒的质量评价,包括外观、粒径、电位、包封率和载药量;
S8、考察大黄素联合索拉非尼纳米制剂在抑制HepG2细胞增殖中的作用。
在进一步的技术方案中,步骤S1中包括以下步骤:
制备大黄素溶液,精密吸取0.2mL的大黄素溶液并对其进行稀释;索拉非尼溶液,精密吸取0.2mL的索拉非尼溶液并对其进行稀释;大黄素混合索拉非尼溶液,2mL的10μg/mL大黄素溶液与2mL的10μg/mL索拉非尼溶液混合均匀即可。
在进一步的技术方案中,步骤S2中包括,以甲醇溶液为空白对照在190~600nm波长范围内使用紫外分光光度计对标准溶液分别进行波长扫描。
在进一步的技术方案中,步骤S3中包括,精密称取大黄素储备液0.4、0.8、1.0、1.4、1.6mL置10mL容量瓶中,甲醇溶液定容配成浓度为4、8、10、14、16μg/mL的系列标准溶液,以甲醇溶液为空白对照在480nm波长下测定各吸光度值。
在进一步的技术方案中,步骤S4中包括,测定的吸光度值与药物浓度进行线性回归,得线性方程为Y=0.0322X+0.0579(r=0.9991)。
在进一步的技术方案中,制备大黄素联合索拉非尼纳米粒包括,称取适量大黄素和索拉非尼与载体材料,加入二氯甲烷-丙酮溶液1.2mL,索拉非尼和大黄素与载体材料完全溶解后,加入2mL 1%PVA溶液,探头超声1min(5s/5s),再加入3mL PVA溶液,探头超声1min(5s/5s)后,转移到茄形瓶中;于37℃水浴条件下旋蒸15min以除去有机溶剂,得到Emo@Sora-NPs胶体溶液,用超纯水定容至5mL后转移至离心管内于4℃避光条件下保存。
在进一步的技术方案中,步骤S7中包括,计算包封率和载药量,其中,包封率(EE)=纳米粒包载药物的质量/投药量×100%;载药量(DL)=纳米粒包载药物的质量/载药纳米的总质量×100%。
在进一步的技术方案中,步骤S8中包括,采用MTT法进行细胞活性检测,并计算细胞的存活率;其中,细胞存活率计算公式如下:细胞存活率(%)=[实验组(OD)-空白组(OD)]/[对照组(OD)-空白组(OD)]×100%。
本发明的有益效果是:
1、聚乙二醇-聚乳酸-羟基乙酸(mPEG-PLGA)由PEG和PLGA通过化学键聚合成两亲性共聚物,是纳米给药系统中的一种载体材料,具有良好的生物相容性,安全,无毒,体内适用的特点。利用该载体材料制成的制剂,可有效改善亲水性,延长化疗药物在体内循环的时间,提高在作用部位的血药浓度,达到缓释、长效的作用;
2、该方法建立的纳米粒包封率、载药量好,可实现大黄素、索拉非尼同时给药;
3、该方法将索拉非尼与大黄素共同载入纳米粒,通过二者协同作用有效提高了抗癌效果,提高了HepG-2细胞对索拉非尼的敏感性;
4、该方法构建的共载药物纳米粒,是一种优良的递送系统,且步骤简单,制备方法可放大,有望应用于治疗肝癌。
附图说明
图1是本发明实施例所述Emo@Sora-NPs制备流程示意图;
图2是本发明实施例所述大黄素(Emo)、索拉非尼(Sora)UV扫描图及大黄素(Emo)+索拉非尼(Sora)混合物UV扫描图;
图3是本发明实施例所述大黄素(Emo)标准曲线图;
图4是本发明实施例所述大黄素(Emo)与索拉非尼(Sora)专属性色谱图;
图5是本发明实施例所述索拉非尼(Sora)标准曲线图;
图6是本发明实施例所述Emo@Sora-NPs外观,其中Sora-NPs,Emo-NPs为对照制剂;
图7是本发明实施例所述Emo@Sora-NPs粒径分布图;
图8是本发明实施例所述Emo@Sora-NPs电位分布图;
图9是本发明实施例所述Sora-NPs、Emo-NPs与Emo@Sora-NPs对HepG2细胞上肿瘤存活率。
具体实施方式
下面结合附图对本发明的实施例作进一步说明。
实施例:
一种大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,包括以下步骤;
S1、配置标准溶液,其中标准溶液包括:大黄素溶液、索拉非尼溶液和大黄素混合索拉非尼溶液;
S2、对上述标准溶液进行波长扫描;
S3、根据扫描确定大黄素的检测波长,测定不同浓度大黄素标准溶液的吸光度值,根据吸光度值对标准溶液进行线性回归,建立标准曲线;
S4、对索拉非尼溶液、大黄素联合索拉非尼溶液进行专属性考察;
S5、测定不同浓度索拉非尼标准溶液中索拉非尼的含量,建立标准曲线;
S6、制备大黄素联合索拉非尼的纳米粒;
S7、大黄素联合索拉非尼纳米粒的质量评价,包括外观、粒径、电位、包封率和载药量;
S8、考察大黄素联合索拉非尼纳米制剂在抑制HepG2细胞增殖中的作用。
在另外一个实施例中,步骤S1中包括以下步骤:
制备大黄素溶液,精密吸取0.2mL的大黄素溶液并对其进行稀释;索拉非尼溶液,精密吸取0.2mL的索拉非尼溶液并对其进行稀释;大黄素混合索拉非尼溶液,2mL的10μg/mL大黄素溶液与2mL的10μg/mL索拉非尼溶液混合均匀即可。将步骤S1中的大黄素与索拉非尼混合溶液在以甲醇溶液为空白对照在480nm波长下扫描其色谱图。结果明确,大黄素在480nm波长条件下对索拉非尼的色谱峰无干扰。如图4所示。
在另外一个实施例中,步骤S2中包括,以甲醇溶液为空白对照在190~600nm波长范围内使用紫外分光光度计对标准溶液分别进行波长扫描。
在另外一个实施例中,步骤S3中包括,精密称取大黄素储备液0.4、0.8、1.0、1.4、1.6mL置10mL容量瓶中,甲醇溶液定容配成浓度为4、8、10、14、16μg/mL的系列标准溶液,以甲醇溶液为空白对照在480nm波长下测定各吸光度值。
在另一个实施例中,步骤S4、S5中包括,精密称取索拉非尼原料药1mg置10mL容量瓶中,用甲醇溶液定容至刻度线,配制成100μg/mL的溶液。再分别精密称取索拉非尼储0.0625、0.125、0.5、1、2、5mL置10mL容量瓶中,用甲醇溶液定容配成浓度为0.625、1.25、5、10、20、50μg/mL的系列标准溶液,以甲醇溶液为空白对照在480nm波长下在测定峰面积。将峰面积对索拉非尼浓度进行线性回归,测定的吸光度值与药物浓度进行线性回归,得线性方程为Y=0.0322X+0.0579(r=0.9991)。如图5所示。
在另一个实施例中,步骤S4中包括,制备大黄素联合索拉非尼纳米粒包括,称取适量大黄素和索拉非尼与载体材料,加入二氯甲烷-丙酮溶液1.2mL,索拉非尼和大黄素与载体材料完全溶解后,加入2mL 1%PVA溶液,探头超声1min(5s/5s),再加入3mL PVA溶液,探头超声1min(5s/5s)后,转移到茄形瓶中;于37℃水浴条件下旋蒸15min以除去有机溶剂,得到Emo@Sora-NPs胶体溶液,用超纯水定容至5mL后转移至离心管内于4℃避光条件下保存。
在另一个实施例中,制备大黄素联合索拉非尼纳米粒包括,称取适量大黄素和索拉非尼与载体材料,加入二氯甲烷-丙酮溶液1.2mL,索拉非尼和大黄色与载体材料完全溶解后,加入2mL 1%PVA溶液,探头超声1min(5s/5s),再加入3ml PVA溶液,探头超声1min(5s/5s)后,转移到茄形瓶中;于37℃水浴条件下旋蒸15min以除去有机溶剂,得到Emo@Sora-NPs胶体溶液,用超纯水定容至5ml后转移至离心管内于4℃避光条件下保存。如图6所示。
在另外一个实施例中,步骤S7中包括,取200μL载药纳米粒于比色杯中,用去离子水稀释至1mL后混匀,用Nano-ZS90 Malvern测定粒径;取1mL纳米粒混悬液于洁净U形管中,加注过程中避免产生气泡,用Nano-ZS90 Malvern测定Zeta电位。如图7、图8所示。取500μL纳米混悬液于离心管中,10000r/min冷冻离心15min,弃去上清液,得到去除游离药物的纳米粒,再将其定量至2mL,分别用UV法和HPLC法测定大黄素和索拉非尼的含量,计算包封率和载药量,其中,包封率(EE)=纳米粒包载药物的质量/投药量×100%;载药量(DL)=纳米粒包载药物的质量/载药纳米的总质量×100%。
在另一个实施例中,步骤S8中包括,采用MTT法进行细胞活性检测;选取生长良好、对数生长期的细胞用胰酶消化后,用培养液稀释至5×104个/mL的细胞密度,混匀后以每孔100μL将细胞悬液接种在96孔板中,将96孔板置37℃细胞培养箱中培养24h使细胞贴壁;贴壁后分组进行试验,分为大黄素组、索拉非尼组和大黄素混合索拉非尼溶液组,每孔加入100μL含有游离药物的培养介质,培养24h后,加入5mg/mL的MTT溶液10μL继续孵育4h后,完全除去培养介质后,每孔加入150μL DMSO溶液,震荡10min,使用酶标仪在490nm和570nm处测定吸光值,并计算细胞的存活率;其中,细胞存活率计算公式如下:细胞存活率(%)=[实验组(OD)-空白组(OD)]/[对照组(OD)-空白组(OD)]×100%。结果如图9所示。
本发明中的材料与仪器的选择:
大黄素(纯度>96%,阿拉丁试剂有限公司),索拉非尼(纯度>99%,MB1226,大连美仑生物技术有限公司),甲醇(赛默飞世尔科技有限公司),HepG2(由电子科技大学刘贻尧教授赠送),DMEM培养基(GE Healthcare Life Science),FBS(上海源叶生物科技有限公司),SP(Hyclone,美国),MTT(纯度88%,Sigma-Aldrich),胰酶(Hyclone,美国)
紫外可见分光光度计(A590型,上海翱艺仪器有限公司),高效液相仪,超声波细胞粉碎机(JY92-IIN型,宁波新芝生物科技股份有限公司),ZetaSizer Nano ZS90型激光粒度仪(英国Malvern),CO2培养箱(美国Thermo Scientific),酶标仪(美国MolecularDevices),流式细胞仪(美国ACEA)。
大黄素储备液的配制
精密称取大黄素原料药1mg置10mL容量瓶中,用甲醇溶液定容至刻度线,配制成100μg/mL的溶液。
波长扫描
制备大黄素溶液(储备液精密吸取0.2mL稀释至5μg/mL),索拉非尼溶液(储备液精密吸取0.2mL稀释至5μg/mL),大黄素混合索拉非尼溶液(2mL的10μg/mL大黄素溶液与2mL的10μg/mL索拉非尼溶液混合均匀),以甲醇溶液为空白对照在190~600nm波长范围内使用紫外分光光度计进行波长扫描。结果显示,大黄素在480nm波长处有较大吸收,且索拉非尼无干扰,因此选择480nm作为大黄素检测波长。
标准曲线的建立
精密称取适量大黄素储备液0.4、0.8、1.0、1.4、1.6mL置10mL容量瓶中,甲醇溶液定容配成浓度为4、8、10、14、16μg/mL的系列标准溶液,以甲醇溶液为空白对照在480nm波长下测定各吸光度值。将吸光度值A对药物浓度进行线性回归,得线性方程为Y=0.0322X+0.0579(r=0.9991)。结果表明,在4~16μg/mL浓度范围内大黄素浓度与吸光度值的线性关系良好。
索拉非尼含量测定:
色谱条件:色谱柱,C18反相色谱柱(250mm×4.6mm,5μm);流动相:0.05%三乙胺(pH=5.4)-乙腈(40:60);检测波长:265nm;流速:1mL/min;柱温:40℃;进样量:10μL。
索拉非尼储备液配制
精密称取索拉非尼原料药1mg置10mL容量瓶中,用甲醇溶液定容至刻度线,配制成100μg/mL的溶液。
特异性实验:按1.2.2项下制备的索拉非尼溶液,索拉非尼与大黄素混合溶液,按1.3.1项下条件依次进样10μL,记录色谱图。结果显示,大黄素在此条件下对索拉非尼的色谱峰没有干扰。
标准曲线的建立:分别精密称取索拉非尼储0.0625、0.125、0.5、1、2、5mL置10mL容量瓶中,用甲醇溶液定容配成浓度为0.625、1.25、5、10、20、50μg/mL的系列标准溶液,按1.3.1项下条件测定峰面积。将峰面积A对药物浓度进行线性回归,得线性方程为Y=51.99X-1.4928(r=0.9997)。结果表明,在0.625~50μg/mL浓度范围内索拉非尼浓度与峰面积的线性关系良好。
大黄素-索拉非尼纳米粒的制备
称取适量大黄素和索拉非尼与载体材料mPEG-PLGA,加入二氯甲烷-丙酮溶液1.2mL,药物与载体材料完全溶解后,加入2mL 1%PVA溶液,探头超声1min(5s/5s),再加入3ml PVA溶液,探头超声1min(5s/5s)后,转移到茄形瓶中。于37℃水浴条件下旋蒸15min以除去有机溶剂,得到Emo@Sora-NPs胶体溶液,用适量超纯水定容至5ml后转移至离心管内于4℃避光条件下保存。
大黄素-索拉非尼纳米粒理化性质
粒径和电位:取200μL载药纳米粒于比色杯中,用去离子水稀释至1mL后混匀,用Nano-ZS90 Malvern测定粒径。取1mL纳米粒混悬液于洁净U形管中,加注过程中避免产生气泡,用Nano-ZS90 Malvern测定Zeta电位。
所制备的纳米粒粒径309.17(±)2.45nm,分散性好,多相分散系数(PdI)为0.251(±)0.01,Zeta电位为-6.58(±)0.54mV。
大黄素-索拉非尼纳米粒的包封率测定
取500μL纳米混悬液于离心管中,10000r/min冷冻离心15min,弃去上清液,得到去除游离药物的纳米粒,再将其定量至2mL,分别用UV法和HPLC法测定大黄素和索拉非尼的含量,计算得的包封率分别约为80.78(±)0.05%、77.4(±)0.71%,载药量分别约为13(±)0.21%、12.0(±)0.10%。包封率(EE)=纳米粒包载药物的质量/投药量×100%;载药量(DL)=纳米粒包载药物的质量/载药纳米的总质量×100%。
细胞培养:HepG2细胞用含100mL/L胎牛血清的DMEM培养基于37℃、5%CO2培养箱中培养。
药物对HepG2细胞的增殖抑制作用:采用MTT法进行细胞活性检测。将生长良好、对数生长期的细胞用胰酶消化后,用培养液稀释至5×104个/mL的细胞密度,混匀后以每孔100μL将细胞悬液接种在96孔板中,将96孔板置37℃细胞培养箱中培养24h使细胞贴壁。贴壁后分组进行试验,分为对照组、大黄素组、索拉非尼组、联合用药组,每孔加入100μL含有游离药物的培养介质,培养24h后,加入5mg/mL的MTT溶液10μL继续孵育4h后,完全除去培养介质后,每孔加入150μL DMSO溶液,震荡10min,使用酶标仪在490nm和570nm处测定吸光值。每组设定3个复孔,取平均数。细胞存活率计算公式如下:细胞存活率(%)=[实验组(OD)-空白组(OD)]/[对照组(OD)-空白组(OD)]×100%。
以上所述实施例仅表达了本发明的具体实施方式,其描述较为具体和详细,但并不能因此而理解为对本发明专利范围的限制。应当指出的是,对于本领域的普通技术人员来说,在不脱离本发明构思的前提下,还可以做出若干变形和改进,这些都属于本发明的保护范围。
Claims (8)
1.一种大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,其特征在于,包括以下步骤;
S1、配置标准溶液,其中标准溶液包括:大黄素溶液、索拉非尼溶液和大黄素混合索拉非尼溶液;
S2、对上述标准溶液进行波长扫描;
S3、根据扫描确定大黄素的检测波长,测定不同浓度大黄素标准溶液的吸光度值,根据吸光度值对标准溶液进行线性回归,建立标准曲线;
S4、对索拉非尼溶液、大黄素联合索拉非尼溶液进行专属性考察;
S5、测定不同浓度索拉非尼标准溶液中索拉非尼的含量,建立标准曲线;
S6、制备大黄素联合索拉非尼的纳米粒;
S7、大黄素联合索拉非尼纳米粒的质量评价,包括外观、粒径、电位、包封率和载药量;
S8、考察大黄素联合索拉非尼纳米制剂在抑制HepG2细胞增殖中的作用。
2.根据权利要求1所述的大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,其特征在于,步骤S1中包括以下步骤:
制备大黄素溶液,精密吸取0.2mL的大黄素溶液并对其进行稀释;索拉非尼溶液,精密吸取0.2mL的索拉非尼溶液并对其进行稀释;大黄素混合索拉非尼溶液,2mL的10μg/mL大黄素溶液与2mL的10μg/mL索拉非尼溶液混合均匀即可。
3.根据权利要求1所述的大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,其特征在于,步骤S2中包括,以甲醇溶液为空白对照在190~600nm波长范围内使用紫外分光光度计对标准溶液分别进行波长扫描。
4.根据权利要求1所述的大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,其特征在于,步骤S3中包括,精密称取大黄素储备液0.4、0.8、1.0、1.4、1.6mL置10mL容量瓶中,甲醇溶液定容配成浓度为4、8、10、14、16μg/mL的系列标准溶液,以甲醇溶液为空白对照在480nm波长下测定各吸光度值。
5.根据权利要求4所述的大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,其特征在于,步骤S5中测定的吸光度值与药物浓度进行线性回归,得线性方程为Y=0.0322X+0.0579(r=0.9991)。
6.根据权利要求1所述的大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,其特征在于,步骤S6中制备大黄素联合索拉非尼纳米粒包括,称取适量大黄素和索拉非尼与载体材料,加入二氯甲烷-丙酮溶液1.2mL,索拉非尼和大黄素与载体材料完全溶解后,加入2mL 1%PVA溶液,探头超声1min(5s/5s),再加入3mL PVA溶液,探头超声1min(5s/5s)后,转移到茄形瓶中;于37℃水浴条件下旋蒸15min以除去有机溶剂,得到Emo@Sora-NPs胶体溶液,用超纯水定容至5mL后转移至离心管内于4℃避光条件下保存。
7.根据权利要求1所述的大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,其特征在于,步骤S7中包括,计算包封率和载药量,其中,包封率(EE)=纳米粒包载药物的质量/投药量×100%;载药量(DL)=纳米粒包载药物的质量/载药纳米的总质量×100%。
8.根据权利要求1所述的大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法,其特征在于,步骤S8中包括,采用MTT法进行细胞活性检测,并计算细胞的存活率;其中,细胞存活率计算公式如下:细胞存活率(%)=[实验组(OD)-空白组(OD)]/[对照组(OD)-空白组(OD)]×100%。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011199694.8A CN112461716B (zh) | 2020-10-29 | 2020-10-29 | 大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011199694.8A CN112461716B (zh) | 2020-10-29 | 2020-10-29 | 大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN112461716A true CN112461716A (zh) | 2021-03-09 |
CN112461716B CN112461716B (zh) | 2024-03-22 |
Family
ID=74835283
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202011199694.8A Active CN112461716B (zh) | 2020-10-29 | 2020-10-29 | 大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN112461716B (zh) |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20070083302A (ko) * | 2006-02-17 | 2007-08-24 | 바이오스펙트럼 주식회사 | 에모딘을 포함하는 피부주름 개선용 화장료 조성물 |
CN103768012A (zh) * | 2013-12-24 | 2014-05-07 | 浙江凯胜科技有限公司 | 一种姜黄素脂质纳米粒悬浮液或纳米粒的制备方法 |
WO2015161192A1 (en) * | 2014-04-17 | 2015-10-22 | Memorial Sloan Kettering Cancer Center | Fucoidan nanogels and methods of their use and manufacture |
CN105833173A (zh) * | 2016-04-18 | 2016-08-10 | 中山大学 | 冬凌草甲素联合姜黄素在制备白血病治疗药物中的应用 |
CN107049944A (zh) * | 2017-05-14 | 2017-08-18 | 辽宁大学 | 一种可实现索拉非尼和姜黄素同时给药的聚合物胶束及其制备方法 |
CN108283624A (zh) * | 2017-01-10 | 2018-07-17 | 北京化工大学 | 一种索拉非尼纳米脂质体制剂及其制备方法 |
KR101895418B1 (ko) * | 2017-03-13 | 2018-09-05 | 건국대학교 글로컬산학협력단 | 에모딘을 포함하는 소라페니브의 암 치료 효과 증강용 조성물 |
CN110420219A (zh) * | 2019-08-27 | 2019-11-08 | 深圳大学 | 一种用于抗肿瘤的联合用药物及其应用 |
US20200000783A1 (en) * | 2017-02-16 | 2020-01-02 | Distretto Tecnologico Sicilia Micro Nano Sistemi S.A.R.L. | Nanoparticles for controlled release of sorafenib and sorafenib derivatives |
CN110755409A (zh) * | 2019-11-06 | 2020-02-07 | 南方医科大学 | 一种大黄素纳米纤维载药系统及其构建方法和应用 |
-
2020
- 2020-10-29 CN CN202011199694.8A patent/CN112461716B/zh active Active
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20070083302A (ko) * | 2006-02-17 | 2007-08-24 | 바이오스펙트럼 주식회사 | 에모딘을 포함하는 피부주름 개선용 화장료 조성물 |
CN103768012A (zh) * | 2013-12-24 | 2014-05-07 | 浙江凯胜科技有限公司 | 一种姜黄素脂质纳米粒悬浮液或纳米粒的制备方法 |
WO2015161192A1 (en) * | 2014-04-17 | 2015-10-22 | Memorial Sloan Kettering Cancer Center | Fucoidan nanogels and methods of their use and manufacture |
CN105833173A (zh) * | 2016-04-18 | 2016-08-10 | 中山大学 | 冬凌草甲素联合姜黄素在制备白血病治疗药物中的应用 |
CN108283624A (zh) * | 2017-01-10 | 2018-07-17 | 北京化工大学 | 一种索拉非尼纳米脂质体制剂及其制备方法 |
US20200000783A1 (en) * | 2017-02-16 | 2020-01-02 | Distretto Tecnologico Sicilia Micro Nano Sistemi S.A.R.L. | Nanoparticles for controlled release of sorafenib and sorafenib derivatives |
KR101895418B1 (ko) * | 2017-03-13 | 2018-09-05 | 건국대학교 글로컬산학협력단 | 에모딘을 포함하는 소라페니브의 암 치료 효과 증강용 조성물 |
CN107049944A (zh) * | 2017-05-14 | 2017-08-18 | 辽宁大学 | 一种可实现索拉非尼和姜黄素同时给药的聚合物胶束及其制备方法 |
CN110420219A (zh) * | 2019-08-27 | 2019-11-08 | 深圳大学 | 一种用于抗肿瘤的联合用药物及其应用 |
CN110755409A (zh) * | 2019-11-06 | 2020-02-07 | 南方医科大学 | 一种大黄素纳米纤维载药系统及其构建方法和应用 |
Also Published As
Publication number | Publication date |
---|---|
CN112461716B (zh) | 2024-03-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Li et al. | Engineering of cascade-responsive nanoplatform to inhibit lactate efflux for enhanced tumor chemo-immunotherapy | |
Dai et al. | 808 nm near-infrared light controlled dual-drug release and cancer therapy in vivo by upconversion mesoporous silica nanostructures | |
CN111718465B (zh) | 一种聚二硫缩醛及其制备方法和应用 | |
CN112915205B (zh) | 一种抗肿瘤光动力学增敏治疗的光敏剂/酶组合递送系统及其制备方法 | |
Song et al. | Graphene oxide coating core–shell silver sulfide@ mesoporous silica for active targeted dual-mode imaging and chemo-photothermal synergistic therapy against tumors | |
CN104288784B (zh) | 纳米羟基磷灰石‑基因‑药物复合物及制备方法和应用 | |
Zhang et al. | Near infrared light triggered reactive oxygen species responsive nanoparticles for chemo-photodynamic combined therapy | |
Peng et al. | Delivery of miR-320a-3p by gold nanoparticles combined with photothermal therapy for directly targeting Sp1 in lung cancer | |
CN112439065B (zh) | 一种兼具分子靶向/声动力治疗的携氧载药自组装纳米药物及其制备方法 | |
CN114601921B (zh) | 多孔Pt纳米花负载乳酸氧化酶的纳米制剂及其制备和应用 | |
He et al. | Near-infrared light-controllable bufalin delivery from a black phosphorus-hybrid supramolecular hydrogel for synergistic photothermal-chemo tumor therapy | |
Zhang et al. | Lactate-driving Pt nanoflower with positive chemotaxis for deep intratumoral penetration | |
Zhang et al. | Highly stable near-infrared dye conjugated cerasomes for fluorescence imaging-guided synergistic chemo-photothermal therapy of colorectal cancer | |
CN109481404B (zh) | 一种pH敏感咪唑脂质体的制备方法 | |
CN114010799B (zh) | 一种光热协同化疗的靶向可降解纳米药物载体及其制备方法 | |
Wang et al. | Cyclo-γ-polyglutamic acid-coated dual-responsive nanomicelles loaded with doxorubicin for synergistic chemo-photodynamic therapy | |
Duan et al. | A co-delivery nanoplatform for a lignan-derived compound and perfluorocarbon tuning IL-25 secretion and the oxygen level in tumor microenvironments for meliorative tumor radiotherapy | |
Lian et al. | Multi salt strategy based on curcumin pyrimidine derivatives prodrugs: Synthesis, biological activity, in vitro and in vivo imaging, and drug distribution research | |
Wang et al. | Conjugated polymer dots for biocompatible siRNA delivery | |
Li et al. | Photothermal/nitric oxide synergistic anti-tumour therapy based on MOF-derived carbon composite nanoparticles | |
CN112461716A (zh) | 大黄素联合索拉非尼的纳米制剂对HepG2增殖的抑制验证方法 | |
CN104147608A (zh) | 一种聚乙二醇-叶酸修饰的氨基化锂皂石纳米颗粒及其制备和应用 | |
CN105687137A (zh) | 叶酸受体靶向的5-氟尿嘧啶/叶酸脂质体药物及其制备方法和应用 | |
CN101011579B (zh) | 细胞浆靶向壳寡糖-脂肪酸嫁接物载药胶团的应用 | |
Zhang et al. | Multifunctional Cu x S-and DOX-loaded AuNR@ mSiO 2 platform for combined melanoma therapy with inspired antitumor immunity |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |