CN106562925A - 一种多重环境刺激响应型药物控释载体及其应用 - Google Patents
一种多重环境刺激响应型药物控释载体及其应用 Download PDFInfo
- Publication number
- CN106562925A CN106562925A CN201610916052.2A CN201610916052A CN106562925A CN 106562925 A CN106562925 A CN 106562925A CN 201610916052 A CN201610916052 A CN 201610916052A CN 106562925 A CN106562925 A CN 106562925A
- Authority
- CN
- China
- Prior art keywords
- medicine
- controlled release
- release carrier
- medicine controlled
- temperature
- 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.)
- Pending
Links
Classifications
-
- 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
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/04—Acids; Metal salts or ammonium salts thereof
- C08F220/06—Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
- C08F220/36—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate containing oxygen in addition to the carboxy oxygen, e.g. 2-N-morpholinoethyl (meth)acrylate or 2-isocyanatoethyl (meth)acrylate
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/52—Amides or imides
- C08F220/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
- C08F220/36—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate containing oxygen in addition to the carboxy oxygen, e.g. 2-N-morpholinoethyl (meth)acrylate or 2-isocyanatoethyl (meth)acrylate
- C08F220/365—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate containing oxygen in addition to the carboxy oxygen, e.g. 2-N-morpholinoethyl (meth)acrylate or 2-isocyanatoethyl (meth)acrylate containing further carboxylic moieties
Abstract
本发明涉及一种多重环境刺激响应型药物控释载体及其在药物控释方面的应用。所述药物控释载体由功能单体H1和功能单体H2,以H3为交联剂,采用氧化还原体系经自由基聚合而成。该载体具有温度、pH、电刺激响应性,可通过调控单体配比、交联剂用量,改变温度、pH等刺激响应参数,从而调控药物释放速度,可根据不同的病灶环境,选择应用本发明所述载体材料,以达到智能释药的功效,避免传统给药方式药物浓度无法控制、对正常组织或器官毒副作用大等缺点。
Description
技术领域
本发明涉及智能高分子材料和药物缓释领域,具体涉及一种多重环境刺激响应型药物控释载体及其在药物控释方面的应用。
背景技术
癌症严重威胁着人类健康,其非手术治疗方法,尤其是药物化疗成为癌症综合治疗的重要手段之一。近年来,随着新药的不断问世和对化疗理论认识的逐渐深入,癌症药物化疗疗效得到很大提高,但常规药物投药后,药物浓度迅速上升,而经代谢、排泄和降解后又迅速降低,在病灶部位药物浓度不够,血液循环半衰期短,容易与血浆蛋白接触而失活,其药效不能充分利用,需要高剂量注射和反复给药,给患者带来极大痛苦和经济负担,这些无疑是癌症药物化疗方法迫切需要解决的问题。
药物控制释放技术将高分子化合物作为药物载体制成药剂,使药物在受药体内长期维持有效浓度,可解决上述问题,大大提高药物的利用率和使用效果,在医学领域的研究和应用日益受到重视。由于肿瘤内部比正常组织和血液pH值低,温度高,而环境响应性药物载体对病灶部位温度和化学环境的异常变动能自动感知,从而可以自动释放所需量药物,当身体正常时,药物控释系统又恢复原态,重新抑制释放,这使智能型释药系统的研发成为药物控释技术发展的必然趋势。聚异丙基丙烯酰胺(PNIPAAm)是最常用的温敏性高分子,其水溶液的较低临界溶解温度(LCST)为32℃,当温度低于32℃时,PNIPAAm分子链呈伸展状态,亲水基团暴露,表现亲水性,当温度高于32℃时,PNIPAAm分子链收缩,疏水基团暴露,表现疏水性,这种独特的性质使其在温度响应控释药物系统研究方面备受青睐。如Liu等[9]在介孔硅纳米粒子表面接枝PNIPAAm和聚甲基丙烯酸,随后键合叶酸,制备咽喉癌靶向温度/pH双响应凝胶,研究了环境刺激对凝胶释药行为的影响,结果表明,在低温高pH值环境,PNIPAAm分子链伸展,使孔道关闭,阻止药物释放,而在高温低pH值环境,PNIPAAm分子链收缩,使介孔暴露,孔道开放,药物放出。由于肿瘤病灶比正常组织温度高,pH值低,这样抗癌药物在经过血液和正常组织时被封闭在释药系统内,而当到达病灶部位时,由于环境因素的变化使药物释放,从而提高疗效,降低毒副作用。
另一方面,抗癌药物无选择性,口服或静脉注射药物后,药物全身分布,在杀伤肿瘤细胞的同时,对正常细胞和组织也造成伤害,因此如果能将药物直接送至病灶部位,将减少对正常组织的损伤。将药物包封至具有电、磁感应的药物载体,在外加电场或磁场的作用下,将起到靶向给药的作用。为赋予凝胶电学响应性,本作品将电活性离子液体(ILs)引入凝胶体系。离子液体由于具有不挥发、不易燃、可设计性强、导电能力强等优点,掀起了全球范围的研究热潮。当前以天然化合物氨基酸和胆碱形成的离子液体成为“新型绿色”离子液体研究开发的方向。氨基酸是一种无毒的天然化合物,因含有氨基和羧基,既可作为离子液体的阴离子又可作为阳离子,并且具有手性、生物降解性及高生物相容性。胆碱是一种无毒的强碱,容易与各种酸进行中和反应,从而生成相应的胆碱盐,胆碱盐可被生物利用,可彻底有氧降解。胆碱-氨基酸离子液体可通过胆碱与氨基酸的中和反应制得,在合成过程中只引入了水为溶剂,工艺绿色、简单,无需复杂的纯化即可制得高纯度离子液体,并且由于阴阳离子都来自无毒的天然原料,因而将提高离子液体的安全性,增加生物降解性及降低毒性,被认为是最具潜力的“新型绿色”离子液体合成途径之一。本发明通过分子改性,将双键引入离子液体分子结构,与温敏性NIPAAm和pH响应性丙烯酸(AAc),通过自由基聚合,制备兼具电、热、pH响应性的多重环境刺激响应型凝胶,作为药物包封载体,应用于对抗癌药物靶向控制释放方面。
发明内容
本发明的目的在于提供一种具有多重环境刺激响应性的药物控释载体,以及其在药物控释方面的应用,以克服传统给药方式的不足,实现随环境因素的变化,药物可以进行智能释放。
本发明的多重环境刺激响应型药物控释载体,由功能单体H1和功能单体H2,以H3为交联剂,采用氧化还原体系经自由基聚合形成凝胶,对抗癌药物H4进行包封,通过调控环境温度、pH等因素,进行药物的控制释放应用。
所述功能单体H1具有导电性,为氨基酸、胆碱形成的离子液体,与丙烯酸在EDC/NHS体系引入双键而得。
所述功能单体H2具有温度响应性或pH敏感性,为N-异丙基丙烯酰胺或丙烯酸或甲基丙烯酸或其混合物。
所述交联剂H3是化学交联剂或物理交联剂,为N,N-亚甲基双丙烯酰胺或锂皂石或硅酸镁锂或其混合物。
所述抗癌药物H4为阿霉素或紫杉醇。
所述药物载体可通过调控单体配比、交联剂用量,改变温度、pH等刺激响应参数,从而调控药物释放速度。
与现有技术相比,本发明具有以下优势:
(1)将具有导电性、温敏性、pH敏感性的功能单体进行有机组合,制备药物控释载体,赋予其多重功能响应性,可通过调控环境刺激因素,实现药物的控制释放。
(2)可通过改变单体配比、交联剂用量,调控药物载体环境刺激响应参数,适用于多种情况的药物智能释放。
(3)制备方法操作简单,条件温和,原料价廉易得,便于推广。
(4)产品的应用,可克服传统给药方式药物浓度难以控制、药效易流失、对正常组织和器官毒副作用大等缺点,可实现药物在病灶部位的合理释放。
具体实施方案
下面结合具体实施例对本发明做进一步阐述,这些实施例仅用于说明本发明而不用于限制本发明的范围。
实施例1
(1)离子液体的改性:将甘氨酸(Gly)和胆碱(Ch)按摩尔比为1.05∶1溶于去离子水,3℃下反应48h;反应结束后60℃下旋蒸除水,50℃下真空干燥反应产物,得到纯净的胆碱-甘氨酸(Ch-Gly)离子液体。在N-羟基琥珀酰亚胺(NHS)和1-乙基-3-(3-二甲胺丙基)碳二亚胺(EDC)反应体系,通过丙烯酸(AAc)将双键引入Ch-Gly离子液体,使各物质的摩尔比为AAc∶Ch-Gly∶EDC∶NHS=5∶5∶5∶1;反应结束后倒入过量乙醇静置,待沉淀析出完全,离心分离,得到乙烯基胆碱-甘氨酸离子液体单体(Ch-Gly-AAc)。
(2)药物载体的制备:将步骤(1)所述Ch-Gly-AAc和异丙基丙烯酰胺(NIPAAm)按质量比Ch-Gly-AAc∶NIPAAm=1∶1配制成10wt%的水溶液,在氮气保护下,以10wt%的N,N-亚甲基双丙烯酰胺(MBAA)为交联剂,以1wt%过硫酸钾(KPS)/2wt%N,N,N′,N′-四甲基乙二胺(TEMED)为引发体系,室温下进行原位自由基聚合,形成凝胶,制得药物载体。
(3)药物的负载与控制释放:将步骤(2)所述凝胶进行纯化,以打孔器将凝胶切成直径为10mm,厚度为2mm的圆片,浸泡入浓度为0.5mg/mL的盐酸阿霉素水溶液,待达到吸附平衡,将凝胶片真空干燥,获得负载抗癌药物的凝胶,应用于不同温度下体液环境(pH=7.4)对药物的控制释放。
实施例2
(1)离子液体的改性:同实施例1。
(2)药物载体的制备:将步骤(1)所述Ch-Gly-AAc和丙烯酸(AAc)单体按质量比Ch-Gly-AAc∶AAc=1∶4配制成10wt%的水溶液,在氮气保护下,以10wt%的N,N-亚甲基双丙烯酰胺(MBAA)为交联剂,以1wt%过硫酸钾(KPS)/2wt%N,N,N′,N′-四甲基乙二胺(TEMED)为引发体系,室温下进行原位自由基聚合,形成凝胶,制得药物载体。
(3)药物的负载与控制释放:将步骤(2)所述凝胶进行纯化,以打孔器将凝胶切为直径为10mm,厚度为2mm的圆片,浸泡入浓度为0.5mg/mL的盐酸阿霉素水溶液,待达到吸附平衡,将凝胶片真空干燥,获得负载抗癌药物的凝胶,应用于胃液环境(pH=2.0)对药物的控制释放。
实施例3
(1)离子液体的改性:将丝氨酸(Ser)和胆碱(Ch)按摩尔比为1.05∶1溶于去离子水,3℃下反应48h;反应结束后60℃下旋蒸除水,50℃下真空干燥反应产物,得到纯净的胆碱-甘氨酸(Ch-Ser)离子液体。在N-羟基琥珀酰亚胺(NHS)和1-乙基-3-(3-二甲胺丙基)碳二亚胺(EDC)反应体系,通过丙烯酸(AAc)将双键引入Ch-Ser离子液体,使各物质的摩尔比为AAc∶Ch-Ser∶EDC∶NHS=5∶5∶5∶1;反应结束后倒入过量乙醇静置,待沉淀析出完全,离心分离,得到乙烯基胆碱-甘氨酸离子液体单体(Ch-Ser-AAc)。
(2)药物载体的制备:将步骤(1)所述Ch-Ser-AAc和异丙基丙烯酰胺(NIPAAm)单体按质量比Ch-Gly-AAc∶NIPAAm=1∶2配制成10wt%的水溶液,在氮气保护下,以10wt%的N,N-亚甲基双丙烯酰胺(MBAA)为交联剂,以1wt%过硫酸钾(KPS)/2wt%N,N,N′,N′-四甲基乙二胺(TEMED)为引发体系,室温下进行原位自由基聚合,形成凝胶,制得药物载体。
(3)药物的负载与控制释放:将步骤(2)所述凝胶进行纯化,以打孔器将凝胶切为直径为10mm,厚度为2mm的圆片,浸泡入浓度为1.0mg/mL的盐酸阿霉素水溶液,待达到吸附平衡,将凝胶片真空干燥,获得负载抗癌药物的凝胶,应用于不同温度下体液环境(pH=7.4)对药物的控制释放。
实施例4
(1)离子液体的改性:同实施例3。
(2)药物载体的制备:将步骤(1)所述Ch-Ser-AAc和丙烯酸(AAc)单体按质量比Ch-Ser-AAc∶AAc=1∶2配制成10wt%的水溶液,在氮气保护下,以10wt%的N,N-亚甲基双丙烯酰胺(MBAA)为交联剂,以1wt%过硫酸钾(KPS)/2wt%N,N,N′,N′-四甲基乙二胺(TEMED)为引发体系,室温下进行原位自由基聚合,形成凝胶,制得药物载体。
(3)药物的负载与控制释放:将步骤(2)所述凝胶进行纯化,以打孔器将凝胶切为直径为10mm,厚度为2mm的圆片,浸泡入浓度为1.0mg/mL的盐酸阿霉素水溶液,待达到吸附平衡,将凝胶片真空干燥,获得负载抗癌药物的凝胶,应用于肠液环境(pH=8.4)对药物的控制释放。
实施例5
(1)离子液体的改性:同实施例1
(2)药物载体的制备:将步骤(1)所述Ch-Gly-AAc和异丙基丙烯酰胺(NIPAAm)、丙烯酸(AAc)按质量比Ch-Gly-AAc∶NIPAAm∶AAc=1∶2∶2配制成10wt%的水溶液,在氮气保护下,以10wt%的N,N-亚甲基双丙烯酰胺(MBAA)为交联剂,以1wt%过硫酸钾(KPS)/2wt%N,N,N′,N′-四甲基乙二胺(TEMED)为引发体系,室温下进行原位自由基聚合,形成凝胶,制得药物载体。
(3)药物的负载与控制释放:将步骤(2)所述凝胶进行纯化,以打孔器将凝胶切为直径为10mm,厚度为2mm的圆片,浸泡入浓度为2.0mg/mL的盐酸阿霉素水溶液,待达到吸附平衡,将凝胶片真空干燥,获得负载抗癌药物的凝胶,应用于不同温度、胃液、肠液、体液环境对药物的控制释放。
实施例6
(1)离子液体的改性:同实施例3。
(2)药物载体的制备:将步骤(1)所述Ch-Ser-AAc和异丙基丙烯酰胺(NIPAAm)、丙烯酸(AAc)按质量比Ch-Ser-AAc∶NIPAAm∶AAc=1∶2∶2配制成10wt%的水溶液,在氮气保护下,以10wt%的N,N-亚甲基双丙烯酰胺(MBAA)为交联剂,以1wt%过硫酸钾(KPS)/2wt%N,N,N′,N′-四甲基乙二胺(TEMED)为引发体系,室温下进行原位自由基聚合,形成凝胶,制得药物载体。
(3)药物的负载与控制释放:同实施例5。
实施例7
(1)离子液体的改性:同实施例1
(2)药物载体的制备:将步骤(1)所述Ch-Gly-AAc和异丙基丙烯酰胺(NIPAAm)、丙烯酸(AAc)按质量比Ch-Gly-AAc∶NIPAAm∶AAc=1∶3∶1配制成10wt%的水溶液,在氮气保护下,以1wt%的N,N-亚甲基双丙烯酰胺(MBAA)为交联剂,以0.1wt%过硫酸钾(KPS)/2wt%N,N,N′,N′-四甲基乙二胺(TEMED)为引发体系,室温下进行原位自由基聚合,形成凝胶,制得药物载体。
(3)药物的负载与控制释放:将步骤(2)所述凝胶进行纯化,以打孔器将凝胶切为直径为10mm,厚度为2mm的圆片,浸泡入浓度为2.0mg/mL的紫杉醇溶液,待达到吸附平衡,将凝胶片真空干燥,获得负载抗癌药物的凝胶,应用于不同温度、胃液、肠液、体液环境对药物的控制释放。
实施例8
(1)离子液体的改性:同实施例3。
(2)药物载体的制备:将步骤(1)所述Ch-Ser-AAc和异丙基丙烯酰胺(NIPAAm)、丙烯酸(AAc)按质量比Ch-Ser-AAc∶NIPAAm∶AAc=1∶3∶1配制成10wt%的水溶液,在氮气保护下,以1wt%的N,N-亚甲基双丙烯酰胺(MBAA)为交联剂,以0.1wt%过硫酸钾(KPS)/2wt%N,N,N′,N′-四甲基乙二胺(TEMED)为引发体系,室温下进行原位自由基聚合,形成凝胶,制得药物载体。
(3)药物的负载与控制释放:同实施例7。
实施例9
(1)离子液体的改性:同实施例1
(2)药物载体的制备:将步骤(1)所述Ch-Gly-AAc和异丙基丙烯酰胺(NIPAAm)、丙烯酸(AAc)按质量比Ch-Gly-AAc∶NIPAAm∶AAc=1∶1∶3配制成10wt%的水溶液,在氮气保护下,以5wt%的N,N-亚甲基双丙烯酰胺(MBAA)为交联剂,以0.5wt%过硫酸钾(KPS)/2wt%N,N,N′,N′-四甲基乙二胺(TEMED)为引发体系,室温下进行原位自由基聚合,形成凝胶,制得药物载体。
(3)药物的负载与控制释放:将步骤(2)所述凝胶进行纯化,以打孔器将凝胶切为直径为10mm,厚度为2mm的圆片,浸泡入浓度为1.0mg/mL的紫衫醇溶液,待达到吸附平衡,将凝胶片真空干燥,获得负载抗癌药物的凝胶,应用于不同温度、胃液、肠液、体液环境对药物的控制释放。
实施例10
(1)离子液体的改性:同实施例3。
(2)药物载体的制备:将步骤(1)所述Ch-Ser-AAc和异丙基丙烯酰胺(NIPAAm)、丙烯酸(AAc)按质量比Ch-Ser-AAc∶NIPAAm∶AAc=1∶1∶3配制成10wt%的水溶液,在氮气保护下,以5wt%的N,N-亚甲基双丙烯酰胺(MBAA)为交联剂,以0.5wt%过硫酸钾(KPS)/2wt%N,N,N′,N′-四甲基乙二胺(TEMED)为引发体系,室温下进行原位自由基聚合,形成凝胶,制得药物载体。
(3)药物的负载与控制释放:同实施例9。
Claims (7)
1.一种多重环境刺激响应型药物控释载体及其应用,其特征在于由功能单体H1和功能单体H2,以H3为交联剂,采用氧化还原体系经自由基聚合形成凝胶,对抗癌药物H4进行包封,通过调控环境温度、pH等因素,进行药物的控制释放应用。
2.根据权利要求1所述的药物控释载体,其特征在于所述功能单体H1为具有导电性的乙烯基[甘氨酸][胆碱]离子液体或乙烯基[丝氨酸][胆碱]离子液体。
3.根据权利要求1所述的药物控释载体,其特征在于所述功能单体H2为具有温度响应性或pH敏感性的N-异丙基丙烯酰胺或丙烯酸或甲基丙烯酸或其混合物。
4.根据权利要求1所述的药物控释载体,其特征在于所述交联剂H3是化学交联剂或物理交联剂,为N,N-亚甲基双丙烯酰胺或锂皂石或硅酸镁锂或其混合物。
5.根据权利要求1所述的药物控释载体,其特征在于所述抗癌药物H4为阿霉素或紫杉醇。
6.根据权利要求1所述的药物控释载体,其特征在于所述药物载体在温度高于37℃可加快药物释放速率。
7.根据权利要求1所述的药物控释载体,其特征在于所述药物载体可通过调控单体配比、交联剂用量,改变温度、pH等刺激响应参数,从而调控药物释放速度。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610916052.2A CN106562925A (zh) | 2016-10-21 | 2016-10-21 | 一种多重环境刺激响应型药物控释载体及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201610916052.2A CN106562925A (zh) | 2016-10-21 | 2016-10-21 | 一种多重环境刺激响应型药物控释载体及其应用 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106562925A true CN106562925A (zh) | 2017-04-19 |
Family
ID=58533956
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610916052.2A Pending CN106562925A (zh) | 2016-10-21 | 2016-10-21 | 一种多重环境刺激响应型药物控释载体及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN106562925A (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107375935A (zh) * | 2017-08-28 | 2017-11-24 | 重庆大学 | 一种温度敏感型水凝胶纳米药物输送系统 |
CN112083162A (zh) * | 2019-07-16 | 2020-12-15 | 何金星 | 一种测定免疫水平的诊断制剂 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102973488A (zh) * | 2012-12-02 | 2013-03-20 | 复旦大学 | 具有氧化还原/pH双重刺激响应性的纳米水凝胶及其制备方法和应用 |
CN104892949A (zh) * | 2015-05-14 | 2015-09-09 | 复旦大学 | 一种谷胱甘肽/pH双重刺激响应离子交联型聚合物纳米水凝胶及其制备方法和应用 |
CN105295077A (zh) * | 2015-11-26 | 2016-02-03 | 天津工业大学 | 一种温敏型聚离子液体凝胶及其制备方法 |
CN105348454A (zh) * | 2015-11-26 | 2016-02-24 | 天津工业大学 | 一种环境友好型导电凝胶及其制备方法 |
-
2016
- 2016-10-21 CN CN201610916052.2A patent/CN106562925A/zh active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102973488A (zh) * | 2012-12-02 | 2013-03-20 | 复旦大学 | 具有氧化还原/pH双重刺激响应性的纳米水凝胶及其制备方法和应用 |
CN104892949A (zh) * | 2015-05-14 | 2015-09-09 | 复旦大学 | 一种谷胱甘肽/pH双重刺激响应离子交联型聚合物纳米水凝胶及其制备方法和应用 |
CN105295077A (zh) * | 2015-11-26 | 2016-02-03 | 天津工业大学 | 一种温敏型聚离子液体凝胶及其制备方法 |
CN105348454A (zh) * | 2015-11-26 | 2016-02-24 | 天津工业大学 | 一种环境友好型导电凝胶及其制备方法 |
Non-Patent Citations (1)
Title |
---|
李玉宝主编: "《生物医学材料》", 30 September 2003 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107375935A (zh) * | 2017-08-28 | 2017-11-24 | 重庆大学 | 一种温度敏感型水凝胶纳米药物输送系统 |
CN112083162A (zh) * | 2019-07-16 | 2020-12-15 | 何金星 | 一种测定免疫水平的诊断制剂 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Zeng et al. | Targeting regulated cell death in tumor nanomedicines | |
Yu et al. | Triple-layered pH-responsive micelleplexes loaded with siRNA and cisplatin prodrug for NF-Kappa B targeted treatment of metastatic breast cancer | |
Hasegawa et al. | Carbon monoxide-releasing micelles for immunotherapy | |
Cai et al. | Stimuli‐sensitive linear–dendritic block copolymer–drug prodrug as a nanoplatform for tumor combination therapy | |
Khan et al. | Fabrication of {198Au0} radioactive composite nanodevices and their use for nanobrachytherapy | |
JP2004520021A5 (zh) | ||
CN107899066A (zh) | 阳离子多羟基聚合物栓塞微球及其制备方法 | |
CN107375935B (zh) | 一种温度敏感型水凝胶纳米药物输送系统 | |
Zhang et al. | A cascade nanoreactor for enhancing sonodynamic therapy on colorectal cancer via synergistic ROS augment and autophagy blockage | |
Dong et al. | Multifunctionalized gold sub‐nanometer particles for sensitizing radiotherapy against glioblastoma | |
Li et al. | Dual-therapeutics-loaded mesoporous silica nanoparticles applied for breast tumor therapy | |
Jia et al. | Multi-functional self-assembly nanoparticles originating from small molecule natural product for oral insulin delivery through modulating tight junctions | |
CN106562925A (zh) | 一种多重环境刺激响应型药物控释载体及其应用 | |
Peng et al. | Phosphate-Degradable Nanoparticles Based on Metal–Organic Frameworks for Chemo-Starvation-Chemodynamic Synergistic Antitumor Therapy | |
Zhang et al. | Enhanced postoperative cancer therapy by iron-based hydrogels | |
Luo et al. | Multifunctional Calcium–Manganese Nanomodulator Provides Antitumor Treatment and Improved Immunotherapy via Reprogramming of the Tumor Microenvironment | |
Ren et al. | Local drug delivery techniques for triggering immunogenic cell death | |
Nafiujjaman et al. | Biodegradable hollow manganese silicate nanocomposites to alleviate tumor hypoxia toward enhanced photodynamic therapy | |
Tian et al. | Epigenetic platinum complexes breaking the “eat me/don’t eat me” balance for enhanced cancer chemoimmunotherapy | |
CN105085845A (zh) | 一种聚合物、制备方法及聚n-异丙基丙烯酰胺铕配合物胶束 | |
Han et al. | Nanocatalase-based oxygen-generating nanocarriers for active oxygen delivery to relieve hypoxia in pancreatic cancer | |
CN113456614A (zh) | 一种基于plga的粒径可变型抗肿瘤仿生纳米制剂及其制备方法和应用 | |
Diaz-Dussan et al. | Oncogenic epidermal growth factor receptor silencing in cervical carcinoma mediated by dynamic sugar-benzoxaborole polyplexes | |
Zhao et al. | Development of a nano-drug delivery system based on mesoporous silica and its anti-lymphoma activity | |
Fu et al. | Glucose oxidase and metal catalysts combined tumor synergistic therapy: mechanism, advance and nanodelivery system |
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 | ||
WD01 | Invention patent application deemed withdrawn after publication | ||
WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170419 |