CN111166893A - 一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法 - Google Patents
一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法 Download PDFInfo
- Publication number
- CN111166893A CN111166893A CN202010102226.8A CN202010102226A CN111166893A CN 111166893 A CN111166893 A CN 111166893A CN 202010102226 A CN202010102226 A CN 202010102226A CN 111166893 A CN111166893 A CN 111166893A
- Authority
- CN
- China
- Prior art keywords
- graphene quantum
- drug
- gold
- polyethyleneimine
- quantum dot
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 108
- 229940079593 drug Drugs 0.000 title claims abstract description 107
- 229910052737 gold Inorganic materials 0.000 title claims abstract description 89
- 239000010931 gold Substances 0.000 title claims abstract description 89
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 title claims abstract description 88
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 title claims abstract description 84
- DKIDEFUBRARXTE-UHFFFAOYSA-N 3-mercaptopropanoic acid Chemical compound OC(=O)CCS DKIDEFUBRARXTE-UHFFFAOYSA-N 0.000 title claims abstract description 82
- 229910021389 graphene Inorganic materials 0.000 title claims abstract description 82
- 239000002096 quantum dot Substances 0.000 title claims abstract description 81
- 229920002873 Polyethylenimine Polymers 0.000 title claims abstract description 79
- 239000000017 hydrogel Substances 0.000 title claims abstract description 79
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 238000013268 sustained release Methods 0.000 title claims abstract description 13
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 13
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims abstract description 35
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims abstract description 24
- 229960000684 cytarabine Drugs 0.000 claims abstract description 24
- 150000002343 gold Chemical class 0.000 claims abstract description 16
- 230000000638 stimulation Effects 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 53
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 10
- 239000012498 ultrapure water Substances 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 8
- 230000001678 irradiating effect Effects 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- 239000006228 supernatant Substances 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 239000008055 phosphate buffer solution Substances 0.000 claims description 6
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 claims description 5
- 229960002303 citric acid monohydrate Drugs 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 2
- 230000001699 photocatalysis Effects 0.000 abstract description 5
- 230000009467 reduction Effects 0.000 abstract description 5
- 230000009471 action Effects 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 230000035945 sensitivity Effects 0.000 abstract description 2
- 230000000694 effects Effects 0.000 description 21
- 238000000338 in vitro Methods 0.000 description 9
- 206010028980 Neoplasm Diseases 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 230000001186 cumulative effect Effects 0.000 description 8
- 238000002512 chemotherapy Methods 0.000 description 7
- 238000000502 dialysis Methods 0.000 description 6
- 230000009881 electrostatic interaction Effects 0.000 description 5
- 238000007626 photothermal therapy Methods 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 2
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000007669 thermal treatment Methods 0.000 description 2
- PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 description 1
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- -1 anionic nucleic acids Chemical class 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910021393 carbon nanotube Inorganic materials 0.000 description 1
- 239000002041 carbon nanotube Substances 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- OMZSGWSJDCOLKM-UHFFFAOYSA-N copper(II) sulfide Chemical compound [S-2].[Cu+2] OMZSGWSJDCOLKM-UHFFFAOYSA-N 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002539 nanocarrier Substances 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- 238000013269 sustained drug release Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/52—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6903—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B32/00—Carbon; Compounds thereof
- C01B32/15—Nano-sized carbon materials
- C01B32/182—Graphene
- C01B32/184—Preparation
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Materials Engineering (AREA)
- Nanotechnology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法。包括以下步骤:制备石墨烯量子点,制备金/石墨烯量子点,制备装载药物阿糖胞苷的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶。本发明的有益效果是:利用石墨烯量子点的光催化还原特性及静电作用即可得到金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶,制备过程简单方便,且该载药水凝胶具有pH敏感性和光转热性能,可通过pH及近红外光的刺激使药物缓慢释放。
Description
技术领域
本发明涉及一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法,属于材料合成和生物医药领域。
技术背景
在传统上,化疗是治疗多种癌症的主要治疗方法,但化疗通常会伴有严重的副作用。因此,作为一种能有效治疗肿瘤的光热疗法因其具有较高的组织穿透性,无创操作以及对正常组织损伤较小等优点而越来越受到研究者的关注。在此过程中,使用近红外光将肿瘤部位的温度提高到有效的治疗温度,癌细胞因高温而被杀死。最近的临床研究表明,光热疗法除了对癌症具有直接的致死作用外,还可以增强化疗的治疗效果,即热可以促进化疗药物进入肿瘤组织,增加局部药物浓度。因此,合成一种同时具备光热效应和药物化疗双重作用的药物缓释载体显得十分重要。
目前,碳纳米管、石墨烯、银纳米粒子、硫化铜和钯等光热转换纳米材料均已被用作光热疗法的纳米载体。其中,金纳米粒子由于其较高的光热转换率和可同时用于成像的能力而被最广泛地使用。石墨烯量子点因其低毒性、良好的生物相容性和易于修饰性在生物医学工程领域引起了广泛的关注。同时,石墨烯量子点还具有光催化还原的特性,通过该特性,它们可以在一定波长的辐射下催化还原系统中的其他物质。研究人员可以利用这一特性来获得金属单质,例如金和银。聚乙烯亚胺是带正电荷的多胺,因此常被用作载体,通过静电结合阴离子核酸。本发明利用石墨烯量子点的光催化还原特性及静电作用制备得到金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶。利用石墨烯量子点的光催化还原特性,用紫外线照射石墨烯量子点和氯金酸的混合物可以快速方便的得到石墨烯量子点覆盖的金纳米球簇。然后利用石墨烯量子点中–COOH电负性较高的特性,将带正电荷(–NH3 +)的抗癌药物阿糖胞苷负载于金/石墨烯量子点表面,接着利用金可以和硫原子形成金硫键的特性,将带–COOH基团的巯基丙酸引入到金/石墨烯量子点表面,最后在控制介质pH的条件下,利用聚乙烯亚胺中–NH3 +与巯基丙酸中–COO–之间的静电作用对载药的金/石墨烯量子点进行聚乙烯亚胺的交联,从而成功的对金/石墨烯量子点/阿糖胞苷/巯基丙酸进行包封得到金/石墨烯量子点/阿糖胞苷/巯基丙酸/聚乙烯亚胺载药水凝胶。在新合成的载药水凝胶中,由于纳米金具有优异的近红外光转热能力,因此该载药水凝胶可以快速的将光转换成热,利用高温杀死癌细胞,从而构建光热治疗平台;与此同时,热将促进药物的释放,增加药物在肿瘤组织周围的局部浓度,进一步增强化疗的治疗效果。pH对于药物缓释所起的作用体现如下:当pH由7.4变成5.0时,巯基丙酸中–COO–质子化成–COOH,由于聚乙烯亚胺中–NH3 +与巯基丙酸中–COOH之间没有静电作用,从而造成凝胶体系的分解和药物释放量的增加;同理,随着pH的降低,石墨烯量子点中–COOH与阿糖胞苷中–NH3 +之间的静电作用也将变弱,这也会导致药物释放量的增加。
发明内容
本发明的目的是在于提供一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法,利用该复合材料具有pH敏感性和光转热性能,可通过pH及近红外光的刺激使药物缓慢释放。
本发明所述一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法,包括以下步骤:
a、制备石墨烯量子点:将一定量的一水合柠檬酸溶于15mL超纯水中,然后将澄清溶液移入坩埚中,在马弗炉中以一定温度加热一段时间后取出,冷却至室温后溶于超纯水中配置成一定浓度的溶液备用;
b、制备金/石墨烯量子点:将一定量的氯金酸溶液和步骤a制成的石墨烯量子点溶液混合均匀,用紫外光照射一段时间,离心除去上清液即得到金/石墨烯量子点,并配置成一定浓度的溶液备用;
c、制备金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶:将适量阿糖胞苷加入到步骤b制备的金/石墨烯量子点溶液中,在室温25℃下搅拌12小时,离心除去上清液后溶于3mL超纯水中,随后加入一定量的巯基丙酸,在室温25℃下搅拌12小时后加入适量的聚乙烯亚胺,静置后即得到金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶;
进一步地,步骤a中一水合柠檬酸的用量为1~3g,马弗炉加热温度为165~185℃,加热时间为1~3h,配置的石墨烯量子点溶液的浓度为10~30mg/mL。
进一步地,步骤b中氯金酸溶液的用量为1~3mL,浓度为10~30mg/mL,石墨烯量子点溶液的用量为1~3mL,紫外光照射的时间为2~10min,配制的金/石墨烯量子点溶液的浓度为1~2mg/mL。
进一步地,步骤c中阿糖胞苷的用量为5~15mg,金/石墨烯量子点溶液的用量为2~8mL,巯基丙酸的用量为0.05~0.2mL,聚乙烯亚胺的用量为0.5~2g。
本发明的有益效果是:利用石墨烯量子点的光催化还原特性及静电作用即可制备得到金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶,制备过程简单方便,且该载药水凝胶具有pH敏感性和光转热性能,可通过pH及近红外光的刺激使药物缓慢释放。
附图说明
下面结合附图对本实验进一步说明。
图1为实施例一中石墨烯量子点(A)、纳米金(B)、金/石墨烯量子点(C)和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶(D)的透射电镜图。
图2为实施例二中近红外光照射石墨烯量子点、金/石墨烯量子点和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的温度时间响应图。
图3为实施例三中金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶在37℃不同pH值时的体外药物缓释性能图。
图4为实施例四中金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶用近红外光照射和对比例一中未用近红外光照射的体外药物缓释性能图。
图5为实施例五中金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶用近红外光照射和对比例二中未用近红外光照射对HL-60细胞的活性影响图。
具体实施方式
现在结合具体实施例对本发明做进一步说明,以下实施例旨在说明本发明而不是对本发明的进一步限定。
实施例一:
制备金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶包括以下几个步骤:
(1)将2g一水合柠檬酸溶于15mL超纯水中,然后将澄清溶液移入坩埚中,在马弗炉中以175℃加热时间2h后取出,冷却至室温后溶于超纯水中配置成浓度为20mg/mL的石墨烯量子点溶液备用。
(2)将2mL20mg/mL的氯金酸溶液和2mL步骤(1)制成的石墨烯量子点溶液混合均匀,用紫外光照射5min,离心除去上清液即得到金/石墨烯量子点,并配置成浓度为1.5mg/mL的金/石墨烯量子点溶液备用;如将得到的金/石墨烯量子点用超纯水多次洗涤离心除去上清液后得到纳米金。
(3)将10g阿糖胞苷加入到5mL步骤(2)制备的金/石墨烯量子点溶液中,在室温25℃下搅拌12h,离心除去上清液后溶于3mL超纯水中,随后加入0.1mL巯基丙酸,在室温25℃下搅拌12h后加入1g聚乙烯亚胺,静置后即得到金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶;未装载药物的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶的制备除了没有加入药物阿糖胞苷以外,其它步骤均与金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备步骤相同。
实施例一中石墨烯量子点、纳米金、金/石墨烯量子点和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的透射电镜图如图1(A)—(D)所示。从图1(A)中可看出制得的石墨烯量子点分散均匀,粒径分布较为均一,主要分布在8nm左右;图1(B)显示制得的纳米金呈现出球形,且粒径在200nm左右。与(A)和(B)相比,从图1(C)中可以明显看出石墨烯量子点成功的包覆了金。与(C)相比,图1(D)中金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的厚度显著增大,这归因于聚乙烯亚胺成功地将装载药物的金/石墨烯量子点/巯基丙酸包覆。
实施例二:
近红外光照射石墨烯量子点、金/石墨烯量子点和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的温度时间响应图包括以下几个步骤:
石墨烯量子点、金/石墨烯量子点、金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备过程与实施例一相同。
分别将石墨烯量子点、金/石墨烯量子点和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶配成浓度为1.5mg/mL的溶液,并取出5mL溶液分别置于烧杯中,在室温25℃下将温度计测温一侧完全浸入溶液中,用波长为808nm,功率为1W的近红外光激光器在距离烧杯2cm处照射,每隔0.5分钟记录温度计温度,其温度时间响应图如图2所示。
从图2中可以看出,石墨烯量子点在近红外光照射下,其温度几乎不产生变化,而金/石墨烯量子点展现出较好的光热响应,在近红外光照射下其温度在5分钟内从25℃上升到47.6℃。而与金/石墨烯量子点相比,金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶也可以上升到45.9℃,仅相差1.7℃并且升温速率几乎不受影响。也就是说,金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶中的纳米金可以快速的将光转换成热,从而构建光热治疗平台。
实施例三:
金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶在37℃不同pH值时体外药物释放包括以下几个步骤:
金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备过程与实施例一相同。
(1)分别称取20mg金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶,置于透析袋中,并将透析袋分别放于30mL pH不同的磷酸盐缓冲溶液中,在温度为37℃条件下磁力搅拌,进行药物体外释放,磷酸盐缓冲溶液的pH分别为5.0、6.2和7.4,释放12小时。
(2)每隔1小时取一次样,每次取样取出3mL溶液,测定释放出的阿糖胞苷的量,同时补充3mL新鲜的磷酸盐缓冲溶液,阿糖胞苷的浓度使用紫外分光光度计测定在272nm处的特征吸收峰强度,根据朗伯-比尔定律计算得到,根据测定的阿糖胞苷的量计算出不同时间的累积释药百分数,如图3所示。
从图3中可以看出,阿糖胞苷的累积释放量在pH值为5.0、6.2和7.4释放12小时后的累计释药百分数分别为58.62%、26.86%和11.91%,表现出很好的pH响应性能。这是由于当pH由7.4降低为5.0时,巯基丙酸中–COO–质子化成–COOH,由于聚乙烯亚胺中–NH3 +与巯基丙酸中–COOH之间没有静电作用,从而造成凝胶体系的分解,累计释药百分数显著增加;同理,随着pH的降低,石墨烯量子点中–COOH与阿糖胞苷中–NH3 +之间的静电作用也将变弱,这也会导致累计释药百分数的增加。
实施例四:
用近红外光照射条件下金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶体外药物释放包括以下几个步骤:
金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备过程与实施例一相同。
(1)称取20mg金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶置于透析袋中,将透析袋放于30mL pH为5.0的磷酸盐缓冲溶液中,进行磁力搅拌,在初始温度为37℃时进行近红外光照射控制药物释放,进行药物体外释放12小时。
(2)每隔1小时取一次样,每次取样取出3mL溶液,测定释放出的阿糖胞苷的量,同时补充3mL新鲜的磷酸盐缓冲溶液,阿糖胞苷的浓度使用紫外分光光度计测定在272nm处的特征吸收峰强度,根据朗伯-比尔定律计算得到,根据测定的阿糖胞苷的量计算出不同时间的累积释药百分数,如图4所示。
对比例一:
未用近红外光照射条件下金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶体外药物释放包括以下几个步骤:
金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备过程与实施例一相同。
(1)称取20mg金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶置于透析袋中,并将透析袋放入30mLpH值为5.0的磷酸盐缓冲溶液中恒温37℃磁力搅拌,未用近红外光照射,体外释放12小时。
(2)每隔1小时取一次样,每次取样取出3mL溶液,测定释放出的阿糖胞苷的量,同时补充3mL新鲜的磷酸盐缓冲溶液,阿糖胞苷的浓度使用紫外分光光度计测定在272nm处的特征吸收峰强度,根据朗伯-比尔定律计算得到,根据测定的阿糖胞苷的量计算出不同时间的累积释药百分数,如图4所示。
从图4中可以看出,金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶用近红外光照射12小时,累积释药百分数为78.62%,明显高于未用近红外光照射时的累积释药百分数58.62%,这说明金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶可以利用近红外光照射增大药物的释放量。
实施例五:
近红外光刺激条件下金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶对HL-60细胞活性影响测试包括以下几个步骤:
金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备过程与实施例一相同。
将金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶分别配置成浓度为0.39、0.78、1.56、3.12、6.25、12.50、25.00和50.00μg/mL的溶液。然后将HL-60细胞经消化、计数、制成1×105个/mL的细胞悬液,接种于96孔板中,置于37℃,5%CO2培养箱中培养过夜,每孔加入上述浓度的溶液,同时设立阴性对照组及空白组,其中一块板加入溶液后于近红外光照射条件下孵育10分钟,后转至37℃条件下培养,将板置于培养箱中培养12小时后每孔加入10μL CCK8溶液,在细胞培养箱内继续孵育3小时,用酶标仪在450nm下测定吸光值,并计算细胞活性,如图5所示。
对比例二:
未用近红外光刺激条件下金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶对HL-60细胞活性影响测试包括以下几个步骤:
金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备过程与实施例一相同。
金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶和金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶分别配置成浓度为0.39、0.78、1.56、3.12、6.25、12.50、25.00和50.00μg/mL的溶液。然后将HL-60细胞经消化、计数、制成1×105个/mL的细胞悬液,接种于96孔板中,置于37℃,5%CO2培养箱中培养过夜,每孔加入上述浓度的溶液,同时设立阴性对照组及空白组,将板置于培养箱中培养12小时后每孔加入10μL CCK8溶液,在细胞培养箱内继续孵育3小时,用酶标仪在450nm下测定吸光值,并计算细胞活性,如图5所示。
从图5中可以看出,没有装载药物的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶在有近红外光照射时,在50.00μg mL-1时细胞活性为63.02%,相比于未用近红外光照射的85.89%细胞活性显著降低,证明金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶具有良好的光热治疗效果。与金/石墨烯量子点/巯基丙酸/聚乙烯亚胺水凝胶85.89%的细胞活性相比,金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶在同样未用近红外光照射时,在其用量为50.00μg/mL浓度时细胞活性仅为20.75%,对HL-60细胞的抑制作用更为显著,这归因于从载体中释放的药物阿糖胞苷可显著抑制细胞的活性。此外,当金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶也用近红外光照射时,HL-60细胞的活性仅为3.01%,这个结果比该载药水凝胶未用近红外光处理时20.75%的细胞活性下降更加明显,这归因于在用近红外光照射时更多量的阿糖胞苷被释放出来,与图4的体外释药实验结果一致,这说明光热疗法有助于提升化疗效果。这些结果说明金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶对HL-60细胞具有优异的化学-光热联合治疗效果,比单一的化疗或光热疗法效果更好。
Claims (6)
1.一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法,其特征在于:步骤如下:
a、制备石墨烯量子点:将一定量的一水合柠檬酸溶于15mL超纯水中,然后将澄清溶液移入坩埚中,在马弗炉中以一定温度加热一段时间后取出,冷却至室温后溶于超纯水中配置成一定浓度的溶液备用;
b、制备金/石墨烯量子点:将一定量的氯金酸溶液和步骤a制成的石墨烯量子点溶液混合均匀,用紫外光照射一段时间,离心除去上清液即得到金/石墨烯量子点,并配置成一定浓度的溶液备用;
c、制备金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶:将适量阿糖胞苷加入到步骤b制备的金/石墨烯量子点溶液中,在室温25℃下搅拌12h,离心除去上清液后溶于3mL超纯水中,随后加入一定量的巯基丙酸,在室温25℃下搅拌12h后加入适量的聚乙烯亚胺,静置后即得到金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶。
2.根据权利要求1所述一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法,其特征是:所述步骤a中一水合柠檬酸的用量为1~3g,马弗炉加热温度为165~185℃,加热时间为1~3h,配置的石墨烯量子点溶液的浓度为10~30mg/mL。
3.根据权利要求1所述一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法,其特征是:所述步骤b中氯金酸溶液的用量为1~3mL,浓度为10~30mg/mL,石墨烯量子点溶液的用量为1~3mL,紫外光照射的时间为2~10min,配制的金/石墨烯量子点溶液的浓度为1~2mg/mL。
4.根据权利要求1所述一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法,其特征是:所述步骤c中阿糖胞苷的用量为5~15mg,金/石墨烯量子点溶液的用量为2~8mL,巯基丙酸的用量为0.05~0.2mL,聚乙烯亚胺的用量为0.5~2g。
5.根据权利要求1所述一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法,其特征是:制备的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶可应用于磷酸盐缓冲溶液的pH分别为5.0,6.2和7.4条件下的释药。
6.根据权利要求1所述一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法,其特征是:制备的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶可应用于近红外光刺激条件下的释药。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010102226.8A CN111166893B (zh) | 2020-02-19 | 2020-02-19 | 一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010102226.8A CN111166893B (zh) | 2020-02-19 | 2020-02-19 | 一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN111166893A true CN111166893A (zh) | 2020-05-19 |
CN111166893B CN111166893B (zh) | 2022-06-28 |
Family
ID=70646928
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010102226.8A Active CN111166893B (zh) | 2020-02-19 | 2020-02-19 | 一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111166893B (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105477647A (zh) * | 2015-12-02 | 2016-04-13 | 常州大学 | 石墨烯量子点/壳聚糖干凝胶的制备并应用于荧光成像和药物缓释 |
CN106974882A (zh) * | 2017-03-07 | 2017-07-25 | 常州大学 | 一种核壳结构的聚吡咯/介孔二氧化硅/石墨烯量子点纳米复合材料在药物控释中的应用 |
CN108354897A (zh) * | 2018-04-20 | 2018-08-03 | 常州大学 | 一种可用于药物缓释的二氧化硅/聚吡咯/聚(丙烯酰胺-丙烯酸)载药复合凝胶的制备 |
CN109875978A (zh) * | 2019-04-12 | 2019-06-14 | 常州大学 | 一种可用于药物缓释的聚丙烯酸-生育酚琥珀酸酯自组装载药体系的制备方法 |
CN109966253A (zh) * | 2019-03-12 | 2019-07-05 | 常州大学 | 一种具有pH响应的壳聚糖/石墨烯量子点/阿糖胞苷药物缓释系统的制备方法 |
-
2020
- 2020-02-19 CN CN202010102226.8A patent/CN111166893B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105477647A (zh) * | 2015-12-02 | 2016-04-13 | 常州大学 | 石墨烯量子点/壳聚糖干凝胶的制备并应用于荧光成像和药物缓释 |
CN106974882A (zh) * | 2017-03-07 | 2017-07-25 | 常州大学 | 一种核壳结构的聚吡咯/介孔二氧化硅/石墨烯量子点纳米复合材料在药物控释中的应用 |
CN108354897A (zh) * | 2018-04-20 | 2018-08-03 | 常州大学 | 一种可用于药物缓释的二氧化硅/聚吡咯/聚(丙烯酰胺-丙烯酸)载药复合凝胶的制备 |
CN109966253A (zh) * | 2019-03-12 | 2019-07-05 | 常州大学 | 一种具有pH响应的壳聚糖/石墨烯量子点/阿糖胞苷药物缓释系统的制备方法 |
CN109875978A (zh) * | 2019-04-12 | 2019-06-14 | 常州大学 | 一种可用于药物缓释的聚丙烯酸-生育酚琥珀酸酯自组装载药体系的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN111166893B (zh) | 2022-06-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Yang et al. | Recent advances in nanosized metal organic frameworks for drug delivery and tumor therapy | |
CN111388666A (zh) | 一种二维纳米复合材料、其制备方法及其应用 | |
CN111978556B (zh) | 一种硒化zif-67的制备方法及应用 | |
CN112641946A (zh) | 聚多巴胺包裹金纳米复合物及其制备方法与在肿瘤多模态诊疗中的应用 | |
CN105031651B (zh) | 一种酶响应型磁性纳米粒及其制备方法与应用 | |
CN105963696B (zh) | 一种靶向性普鲁士蓝纳米粒子的制备方法及其应用 | |
Qi et al. | Rigid metal/liquid metal nanoparticles: Synthesis and application for locally ablative therapy | |
CN111166893B (zh) | 一种可用于药物缓释的金/石墨烯量子点/巯基丙酸/聚乙烯亚胺载药水凝胶的制备方法 | |
CN108723386A (zh) | 一种具有光热效应的金纳米枝晶颗粒的制备方法 | |
CN109966490B (zh) | 一种可降解锑纳米结构、制备方法及应用 | |
CN107961375B (zh) | 一种金属硫化物纳米材料及其制备方法和应用 | |
CN115227815B (zh) | 一种基于钯钌杂化纳米酶的纳米复合材料及其制备方法和应用 | |
CN116785446A (zh) | 一种CeO2/Fe3O4杂化多孔碳纳米颗粒及其制备 | |
CN106267205B (zh) | 一种金/季碳点核壳纳米复合材料及其制备方法 | |
CN113679837A (zh) | 一种窄带隙无机纳米酶治疗试剂及其制备方法与应用 | |
CN112870355B (zh) | 一种复合纳米多孔的铂基配位聚合物及其制备方法和应用 | |
CN115671312A (zh) | 一种掺杂铜的纳米载体的制备方法及其应用 | |
CN108721249B (zh) | 一种载药金纳米枝晶颗粒的制备方法 | |
CN109157531B (zh) | 一种多孔铋纳米微球及其制备方法和应用 | |
Li et al. | Neutrophil membrane camouflaged hybrid nanozymes for enhanced starvation/photothermal tumor therapy | |
CN113117078A (zh) | 一种肿瘤治疗新药物AuNCs@GTTN及其制备方法和应用 | |
CN111388671A (zh) | 纳米药物载体、包含该纳米药物载体的载药体系及载药体系的制备方法 | |
CN116036270B (zh) | 诊疗一体化的复合磁性半导体纳米材料的制备方法及应用 | |
CN110859965B (zh) | 具有aie特性的多功能纳米粒子及其制备方法与应用 | |
CN107638567A (zh) | 一种金属罗森黑盐及其制备方法和用途 |
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 | ||
EE01 | Entry into force of recordation of patent licensing contract | ||
EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20200519 Assignee: Shandong Zhengtian Electronic Technology Co.,Ltd. Assignor: CHANGZHOU University Contract record no.: X2024980010523 Denomination of invention: A preparation method of gold/graphene quantum dots/mercaptopropionic acid/polyethyleneimine drug loaded hydrogel for drug sustained release Granted publication date: 20220628 License type: Common License Record date: 20240724 |