CN103110957B - Graphene oxide drug carrier as well as preparation method and application thereof - Google Patents
Graphene oxide drug carrier as well as preparation method and application thereof Download PDFInfo
- Publication number
- CN103110957B CN103110957B CN201310067067.2A CN201310067067A CN103110957B CN 103110957 B CN103110957 B CN 103110957B CN 201310067067 A CN201310067067 A CN 201310067067A CN 103110957 B CN103110957 B CN 103110957B
- Authority
- CN
- China
- Prior art keywords
- graphene oxide
- pharmaceutical carrier
- serum albumin
- human serum
- preparation
- 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.)
- Expired - Fee Related
Links
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a graphene oxide drug carrier as well as a preparation method and an application thereof. A monolayer or multilayer graphene oxide of human serum albumin is combined to serve as a transport carrier of the drug, and active ingredients of the drug are loaded by absorption. The drug carrier is simple in preparation, good in biocompatibility and very low in cytotoxicity, so that the drug carrier has a wide application prospect in a clinical application, and particularly in malignant tumor treatment aspect.
Description
Technical field
The invention belongs to nano-medicament carrier field, be specifically related to a kind of graphene oxide pharmaceutical carrier and its preparation method and application.
Background technology
Pharmaceutical carrier refers to can carrying medicament and can change the system that medicine enters the rate of release of the mode in body and distribution in vivo, control medicine and conducts drugs to target organs.Nanotechnology is one of current study hotspot, and its core is exactly to utilize the property of nano material to realize general material be beyond one's reach function and purposes.Nano material can freely enter cell, and is enriched in tumor tissues.Utilize the particularity of nano material, with Drug combination, can reduce the using dosage of medicine, and make it have corresponding targeting.Human serum albumin is the strand sugar based protein being made up of 585 amino acid residues, have in conjunction with, transport endogenous and exogenous material and maintain blood plasma pH, colloid osmotic pressure and the physiologically active such as stablize, possess good biocompatibility, biodegradability, bioavailability.Human serum albumin combines with antitumor drug, can realize initiatively targeting by being combined with the specific receptor of vascular endothelial cell and tumor cell surface, and reduce the toxic and side effects of antitumor drug.
The problem such as conventional medicament carrier often exists that drug loading is low, complicated process of preparation, poor stability, cytotoxicity are large.And the size of conventional medicament carrier is larger, make it be difficult to circulate drug delivery to target tissue by mucosa or body.Therefore, be necessary to develop one and prepare simply, drug loading, stability and biocompatibility be gratifying novel nano medicament transport carrier all.
Summary of the invention
The object of the present invention is to provide a kind of graphene oxide pharmaceutical carrier and its preparation method and application; this be a kind of simple, fast, power consumption less, be easy to the method for preparing Organic Nano-Scale Pharmaceutical Carrier of scale; the graphene oxide pharmaceutical carrier that the method is made; a kind of new medicine controlled releasing mode and approach are provided; can significantly improve the bioavailability of medicine; reduce the toxic and side effects of medicine, improve the therapeutic effect of medicine.
For achieving the above object, the present invention adopts following technical scheme:
A kind of graphene oxide pharmaceutical carrier is the human serum albumin that absorption has biocompatibility on graphene oxide, as the transport agent of medicine, by adsorption carrying medicament active component.Described graphene oxide is the single or multiple lift graphene oxide of diameter 10 nm – 2 μ m.Concrete steps are as follows:
(1) taking water as solvent, preparation graphene oxide suspension, concentration is 1 μ g/mL ~ 100 mg/mL;
(2) taking water as solvent, preparation human serum albumin aqueous solution, concentration is 1 μ g/mL ~ 100 mg/mL;
(3) step (1) solution is fully mixed with step (2) solution;
(4) in step (3) mixed liquor, add at least one medicine, fully stirring and evenly mixing;
(5) by step (4) mixed liquor ultrafiltration, collecting precipitation thing, 2 ~ 8 DEG C of cold preservations.
Described active constituents of medicine comprises anticarcinogen, antibiotic, hormone, hormone antagonist, interleukin, interferon, somatomedin, tumor necrosis factor, endotoxin, lymphotoxin, urokinase, streptokinase, tissue plasminogen activator, protease inhibitor, alkyl phosphate choline, labelled with radioisotope composition, antisense DNA, little RNA, antibody, optical dynamic therapy medicine, medicine for cardiovascular system, gastrointestinal system medicine, one or more mixture in drugs for nervous.
Described anticarcinogen comprises in paclitaxel, camptothecine, phthalocyanine, epirubicin, docetaxel, gemcitabine, cisplatin, carboplatin, taxol, procarbazine, cyclophosphamide, actinomycin D, daunorubicin, etoposide, tamoxifen, amycin, mitomycin, bleomycin, plicamycin, anti-platinum, vinblastine, methotrexate one or more mixture.
Described active constituents of medicine has 0 to 100% the load mark calculating as equation 1:
Load mark (%)=
(1)
Pharmaceutical carrier of the present invention can be used for the treatment of disease.The disease of application pharmaceutical carrier of the present invention comprises gastric cancer, pulmonary carcinoma, breast carcinoma, ovarian cancer, hepatocarcinoma, bronchogenic carcinoma, nasopharyngeal carcinoma, laryngeal carcinoma, cancer of pancreas, bladder cancer, colon cancer and cervical cancer.The kind of the active constituents of medicine comprising in pharmaceutical carrier of the present invention can change according to desired application.That is to say, pharmaceutical carrier of the present invention can be used in multiple medical applications.
The invention still further relates to the pharmaceutical composition that comprises described pharmaceutical carrier and at least one pharmaceutically suitable carrier.For being carried on the kind of the active constituents of medicine in pharmaceutical composition of the present invention and the kind of the applied disease of pharmaceutical composition of the present invention is not particularly limited, for example, they are identical with those in pharmaceutical carrier of the present invention.Be not particularly limited for the kind that can be used for the carrier in described pharmaceutical composition.General carrier and excipient available in medical application all can be used in the present invention, their instantiation includes but not limited to, ion exchange resin, aluminium oxide, aluminium stearate, lecithin, serum albumin, buffer substance, water, salt and electrolyte, silica sol, magnesium trisilicate, PVP, based on cellulosic substrate, Polyethylene Glycol, sodium carboxymethyl cellulose, polyacrylic, wax and lanoline.Pharmaceutical composition of the present invention also can comprise and be selected from, but is not limited to, at least one additive of lubricant, wetting agent, emulsifying agent, suspending agent and antiseptic.Pharmaceutical carrier of the present invention or pharmaceutical composition can be prepared into various dosage forms, for example, include, but not limited to water-soluble solution, aseptic injection preparation that parenteral is used.
Remarkable advantage of the present invention is:
(1) pharmaceutical carrier preparation is simple.Whole process does not relate to chemical reaction.
(2) pharmaceutical carrier toxicity is little.Graphene oxide and human serum albumin itself do not have toxicity substantially to cell, has good biology safety.
(3) can realize the harmless loading of medicine activity component.Graphene oxide and human serum albumin pass through suction type bound drug molecule, thereby have avoided the damage of covalent bonding to drug molecular structure.
(4) can realize medicament slow release.Because medicine is carried on pharmaceutical carrier with suction type, its active component is easy to discharge from pharmaceutical carrier, and keeps rate of release slowly, is conducive to keep for a long time drug effect.
(5) can realize target administration.Human serum albumin combines with antitumor drug, can realize initiatively targeting by being combined with the specific receptor of vascular endothelial cell and tumor cell surface, can reduce the toxic and side effects of antitumor drug simultaneously.
Brief description of the drawings
The survival rate of HeLa cell when Fig. 1 is variable concentrations GO-HSA;
The survival rate of HeLa cell when Fig. 2 is variable concentrations GO-HSA-DOX, DOX;
Fig. 3 is that GO-HSA-DOX is respectively at the pH DOX release rate of 7.4,5.5 o'clock.
Detailed description of the invention
The following examples will further be illustrated for the present invention, and will serve as content of the present invention.But these embodiment should not be considered as limiting the scope of the present invention.
Embodiment 1
The preparation of graphene oxide (GO)
0.2 g carbon black adds 50 ml HNO
3(the dense HNO of 25 ml
3add 25 ml water), 130 DEG C of reflux 24 h, be cooled to centrifugal 10 min of 8000 rpm after room temperature, getting supernatant is heated to 150 DEG C of evaporations and obtains bronzing solid, in solid, add 4 ml water mix homogeneously to obtain red tan solution, with to see through molecular weight be 3500 bag filter dialyses 24 h, take out liquid in bag filter and add Na
2cO
3pH is adjusted to neutrality by solution, then continue, by interior liquid 3 d that dialyse, to obtain graphene oxide solution, be stored in 4 DEG C for subsequent use.
Embodiment 2
Graphene oxide-human serum albumin's (GO-HSA) preparation, stability and cytotoxicity
GO mixes after concussion 1 h with mass ratio 1:5 with HSA, and GO-HSA is placed in respectively to H
2in O, PBS, 1640 cell culture fluids, calf serum, making final concentration is 400 μ g/ml, after centrifugal 10 min of 12000 rpm, has no precipitation, and the GO-HSA in each solvent is still uniformly dispersed, and has good stability.HeLa cell is inoculated in 96 orifice plates, after 24 h, GO-HSA is added in orifice plate and form Concentraton gradient, add culture medium to cultivate simultaneously, after 24 h, add MTT dyestuff, after 3.5 h, add DMSO mix homogeneously, after 10 min, read OD value with reading plate device.Result as shown in Figure 1, even can find out that the GO-HSA of high concentration is also nontoxic to cell substantially.
Embodiment 3
Preparation and the cytotoxicity of graphene oxide-human serum albumin-amycin (GO-HSA-DOX)
GO-HSA and DOX are mixed after concussion 1 h with mass ratio 1:5:1, and ultrafiltration is to remove unconjugated DOX, and precipitation is uniformly dissolved again with PBS, is put in 4 DEG C of refrigerators for subsequent use.HeLa cell is inoculated in 96 orifice plates, after 24 h, GO-HSA-DOX is added in orifice plate and form Concentraton gradient, add culture medium to cultivate simultaneously, after 24 h, add MTT dyestuff, after 3.5 h, add DMSO mix homogeneously, after 10min, read OD value with reading plate device.Result as shown in Figure 2, can find out that GO-HSA-DOX generally kills the better effects if of cancerous cell than simple DOX.
Embodiment 4
The release of amycin (DOX)
Will GO-HSA-DOX dissolve 30,60,120,240,360, carry out ultrafiltration after 480min with pH=7.4,5.5 PBS respectively, survey the fluorescent value of filtrate, calculate the DOX release rate in pH=7.4,5.5 PBS respectively.Result as shown in Figure 3, can find out that (pH=5.5) GO-HSA-DOX more can continue, discharge slowly more DOX under acid condition.Thus infer, in the sour environment of tumor tissues GO-HSA-DOX can continue, slow release DOX.
The foregoing is only preferred embodiment of the present invention, all equalizations of doing according to the present patent application the scope of the claims change and modify, and all should belong to covering scope of the present invention.
Claims (5)
1. a graphene oxide pharmaceutical carrier, is characterized in that: on graphene oxide, absorption has the human serum albumin of biocompatibility, as the transport agent of medicine, by adsorption carrying medicament active component; Described pharmaceutically active becomes amycin.
2. graphene oxide pharmaceutical carrier according to claim 1, is characterized in that: described graphene oxide is the single or multiple lift graphene oxide of diameter 10 nm – 2 μ m.
3. a method of preparing graphene oxide pharmaceutical carrier as claimed in claim 1, is characterized in that: graphene oxide solution is fully mixed with human serum albumin solution, human serum albumin is combined closely in graphene oxide surface.
4. the preparation method of graphene oxide pharmaceutical carrier according to claim 3, is characterized in that: the concentration of graphene oxide solution is 1 μ g/mL ~ 100 mg/mL, and human serum albumin solution's concentration is 1 μ g/mL ~ 100 mg/mL.
5. graphene oxide pharmaceutical carrier as claimed in claim 1, in an application of preparing in cancer therapy drug, is characterized in that: amycin is adsorbed in graphene oxide and human serum albumin surface.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310067067.2A CN103110957B (en) | 2013-03-04 | 2013-03-04 | Graphene oxide drug carrier as well as preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310067067.2A CN103110957B (en) | 2013-03-04 | 2013-03-04 | Graphene oxide drug carrier as well as preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103110957A CN103110957A (en) | 2013-05-22 |
| CN103110957B true CN103110957B (en) | 2014-12-03 |
Family
ID=48409365
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310067067.2A Expired - Fee Related CN103110957B (en) | 2013-03-04 | 2013-03-04 | Graphene oxide drug carrier as well as preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103110957B (en) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103784407B (en) * | 2014-02-26 | 2016-01-20 | 哈尔滨医科大学 | Graphene oxide-loaded adriamycin nano-particles of a kind of folate-mediated PEG-and preparation method thereof |
| TWI543778B (en) * | 2014-09-30 | 2016-08-01 | 國立交通大學 | Protein-graphene nanocomposite drug carrier |
| CN105669827B (en) * | 2014-11-20 | 2019-04-09 | 中国科学院高能物理研究所 | Purposes and a kind of protein separating method of the graphene oxide as protein adsorbing medium material |
| CN104692343B (en) * | 2015-03-17 | 2017-01-25 | 福州大学 | Tin selenide nano material, preparation method and application thereof |
| CN105195106A (en) * | 2015-09-15 | 2015-12-30 | 李云峰 | Graphene oxide-recombinant streptococcal protein A composite material as well as preparation method and application thereof |
| CN106039321A (en) * | 2016-05-27 | 2016-10-26 | 中南大学湘雅医院 | Rituximab/graphene oxide composite antibody as well as preparation method and application thereof |
| CN107796791B (en) * | 2016-08-31 | 2020-08-25 | 陕西师范大学 | Method for screening Rev polypeptide small molecule antagonist based on graphene oxide |
| CN106421804B (en) * | 2016-10-21 | 2019-09-03 | 曲阜师范大学 | A kind of fluorinated graphene nano-medicament carrier and its preparation method and application |
| CN108478802B (en) * | 2018-04-02 | 2020-05-22 | 浙江工业大学 | High-stability combined drug delivery system for cancer treatment and construction method |
| CN110025814B (en) * | 2019-04-23 | 2021-07-06 | 国家纳米科学中心 | Application of graphene oxide, dressing containing graphene oxide and anti-tumor particles |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102232933A (en) * | 2011-06-29 | 2011-11-09 | 清华大学 | Tumor-targeting albumin nano-lyophilized powder injection preparation and preparation method thereof |
| CN102274521A (en) * | 2011-08-25 | 2011-12-14 | 天津医科大学 | Graphene oxide-based target gene vector material and preparation and use thereof |
| CN102552932A (en) * | 2012-02-09 | 2012-07-11 | 哈尔滨工业大学 | Method for preparing graphene oxide double-targeting medicine carrier material, and loaded medicine |
-
2013
- 2013-03-04 CN CN201310067067.2A patent/CN103110957B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102232933A (en) * | 2011-06-29 | 2011-11-09 | 清华大学 | Tumor-targeting albumin nano-lyophilized powder injection preparation and preparation method thereof |
| CN102274521A (en) * | 2011-08-25 | 2011-12-14 | 天津医科大学 | Graphene oxide-based target gene vector material and preparation and use thereof |
| CN102552932A (en) * | 2012-02-09 | 2012-07-11 | 哈尔滨工业大学 | Method for preparing graphene oxide double-targeting medicine carrier material, and loaded medicine |
Non-Patent Citations (3)
| Title |
|---|
| 《盐酸阿霉素在纳米载体氧化石墨烯上的可控负载与释放》;李晓;《功能材料》;20130131;第44卷;第96页摘要，右栏"2.2" * |
| 崔瑜霞.《白蛋白在靶向给药以及长效给药系统的研究进展》.《2011年中国药学大会暨第11届中国药师周论文集》.2011,第1段. * |
| 李晓.《盐酸阿霉素在纳米载体氧化石墨烯上的可控负载与释放》.《功能材料》.2013,第44卷第96页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103110957A (en) | 2013-05-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103110957B (en) | Graphene oxide drug carrier as well as preparation method and application thereof | |
| Lin et al. | GSH-responsive SN38 dimer-loaded shape-transformable nanoparticles with iRGD for enhancing chemo-photodynamic therapy | |
| Li et al. | Curcumin-loaded redox-responsive mesoporous silica nanoparticles for targeted breast cancer therapy | |
| JP6677914B2 (en) | Specific targeted biodegradable amphiphilic polymers for ovarian cancer, polymer vesicles prepared therefrom and uses thereof | |
| Li et al. | Hyaluronic acid-modified manganese dioxide-enveloped hollow copper sulfide nanoparticles as a multifunctional system for the co-delivery of chemotherapeutic drugs and photosensitizers for efficient synergistic antitumor treatments | |
| CN105708848A (en) | Environmentally responsive tumor targeted combined administration transfer system | |
| CN105056233A (en) | Multifunctional mesoporous silica nanoparticles having near-infrared photothermal and in-vivo fluorescence imaging characteristics as well as preparation method and application of mesoporous silica nanoparticles | |
| Cao et al. | Surface PEGylation of MIL-101 (Fe) nanoparticles for co-delivery of radioprotective agents | |
| CN106265510A (en) | Multistage target polymer micelle of pH trigger-type release and preparation method thereof in a kind of tumor cell | |
| Chen et al. | Co-delivery of hydrophilic/hydrophobic drugs by multifunctional yolk-shell nanoparticles for hepatocellular carcinoma theranostics | |
| CN105030795A (en) | Nanometer drug-loading system as well as preparation method and application thereof | |
| Shi et al. | Biofilm-encapsulated nano drug delivery system for the treatment of colon cancer | |
| Ye et al. | In situ generation of gold nanoparticles on bacteria‐derived magnetosomes for imaging‐guided starving/chemodynamic/photothermal synergistic therapy against cancer | |
| Wen et al. | Erythrocyte membrane-camouflaged gefitinib/albumin nanoparticles for tumor imaging and targeted therapy against lung cancer | |
| Li et al. | Anti-tumor efficacy of folate modified PLGA-based nanoparticles for the co-delivery of drugs in ovarian cancer | |
| Moharramnejad et al. | A review of recent developments of metal–organic frameworks as combined biomedical platforms over the past decade | |
| CN101951956A (en) | Drug delivery system for administration of poorly water soluble pharmaceutically active substances | |
| Mdlovu et al. | In vitro intracellular studies of pH and thermo-triggered doxorubicin conjugated magnetic SBA-15 mesoporous nanocarriers for anticancer activity against hepatocellular carcinoma | |
| Li et al. | Functionalized magnetic nanoparticles for drug delivery in tumor therapy | |
| Xing et al. | Janus nanocarriers for magnetically targeted and hyperthermia-enhanced curcumin therapy of liver cancer | |
| Li et al. | Nanodiamond-based multifunctional platform for oral chemo-photothermal combinational therapy of orthotopic colon cancer | |
| Hofferberth et al. | Nanotechnology applications in thoracic surgery | |
| CN105859990A (en) | Polymer with side chains containing lipoyl, preparation method of polymer, polymer vesica prepared from polymer and application of polymer vesica | |
| Cui et al. | A novel ligand-modified nanocomposite microparticles improved efficiency of quercetin and paclitaxel delivery in the non-small cell lung cancer | |
| Tian et al. | Recent advances in hydrogels-based osteosarcoma therapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20141203 Termination date: 20190304 |