CN103083222A - 一锅法制备三组分聚合物胶束 - Google Patents
一锅法制备三组分聚合物胶束 Download PDFInfo
- Publication number
- CN103083222A CN103083222A CN2011103354235A CN201110335423A CN103083222A CN 103083222 A CN103083222 A CN 103083222A CN 2011103354235 A CN2011103354235 A CN 2011103354235A CN 201110335423 A CN201110335423 A CN 201110335423A CN 103083222 A CN103083222 A CN 103083222A
- Authority
- CN
- China
- Prior art keywords
- micelle
- add
- preparation
- daa
- alginic acid
- 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
- 239000000693 micelle Substances 0.000 title claims abstract description 66
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 229920000642 polymer Polymers 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title claims abstract description 4
- 238000005580 one pot reaction Methods 0.000 title abstract 2
- 239000003814 drug Substances 0.000 claims abstract description 21
- 229940079593 drug Drugs 0.000 claims abstract description 15
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims abstract description 11
- 235000010443 alginic acid Nutrition 0.000 claims abstract description 11
- 229920000615 alginic acid Polymers 0.000 claims abstract description 11
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 11
- 229960001680 ibuprofen Drugs 0.000 claims abstract description 11
- 239000000783 alginic acid Substances 0.000 claims abstract description 10
- 229960001126 alginic acid Drugs 0.000 claims abstract description 10
- 150000004781 alginic acids Chemical class 0.000 claims abstract description 10
- QZIQJVCYUQZDIR-UHFFFAOYSA-N mechlorethamine hydrochloride Chemical compound Cl.ClCCN(C)CCCl QZIQJVCYUQZDIR-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 4
- 238000007334 copolymerization reaction Methods 0.000 claims abstract description 3
- 238000006116 polymerization reaction Methods 0.000 claims abstract 2
- 238000003756 stirring Methods 0.000 claims description 15
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 9
- 239000012498 ultrapure water Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 239000000661 sodium alginate Substances 0.000 claims description 6
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 5
- 239000008367 deionised water Substances 0.000 claims description 5
- 229910021641 deionized water Inorganic materials 0.000 claims description 5
- 235000010413 sodium alginate Nutrition 0.000 claims description 5
- 229940005550 sodium alginate Drugs 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 238000000502 dialysis Methods 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 3
- 239000003999 initiator Substances 0.000 claims description 3
- 239000000178 monomer Substances 0.000 claims description 3
- 239000002105 nanoparticle Substances 0.000 claims description 3
- 230000007935 neutral effect Effects 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 230000035945 sensitivity Effects 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- 238000010792 warming Methods 0.000 claims description 3
- 230000020477 pH reduction Effects 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 239000003960 organic solvent Substances 0.000 abstract description 3
- OMNKZBIFPJNNIO-UHFFFAOYSA-N n-(2-methyl-4-oxopentan-2-yl)prop-2-enamide Chemical compound CC(=O)CC(C)(C)NC(=O)C=C OMNKZBIFPJNNIO-UHFFFAOYSA-N 0.000 abstract 4
- JKNCOURZONDCGV-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-methylprop-2-enoate Chemical compound CN(C)CCOC(=O)C(C)=C JKNCOURZONDCGV-UHFFFAOYSA-N 0.000 abstract 1
- 239000007864 aqueous solution Substances 0.000 abstract 1
- 238000005538 encapsulation Methods 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000004962 physiological condition Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000008366 buffered solution Substances 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 238000011275 oncology therapy Methods 0.000 description 2
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
- 229960001756 oxaliplatin Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229920000867 polyelectrolyte Polymers 0.000 description 2
- 230000003578 releasing effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 229930195573 Amycin Natural products 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 239000003519 biomedical and dental material Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000002189 fluorescence spectrum Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229920001187 thermosetting polymer Polymers 0.000 description 1
Images
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
一锅法制备三组分聚合物胶束。一种制备胶束的新方法，属于生物医用材料技术领域。本发明将海藻酸、甲基丙烯酸-2-(N，N-二甲基)氨基乙酯(DEMA)和双丙酮丙烯酰胺(DAA)在水溶液中进行聚合.制备胶束。通过DEMA和DAA共聚形成胶束的核，海藻酸中的羧基与PDEMA中氨基之间的静电引力形成胶束的壳。通过改变DAA的含量，研究胶束的结构及性能的变化，结果表明当三种组分的摩尔比为1∶1∶0.5(ADD-05)时效果最好，所得胶束形貌规整、粒径分布最窄，对疏水性药物布洛芬的载药率和包封率最高。本发明优点是：胶束制备方法简单、不使用有机溶剂、生物相容性好、可生物降解。胶束可以提高对疏水性药物的负载量，在模拟人体生理条件下具有良好的缓释效果。
Description
技术领域
本研究涉及由三组分聚合物进行胶束的制备，属于生物医用材料技术领域。
背景技术
双亲性共聚物在水中通过自组装可以形成纳米胶束，通常情况下双亲性共聚物的合成需要用到有机溶剂，合成复杂，成本较高。近年来，将天然高分子制备成胶束用作药物载体引起了人们的广泛关注。具有纳米尺寸的胶束具有超微小体积，能穿过组织间隙并被细胞吸收，且能够避免被吞噬细胞清除掉，使其在药物和基因输送方面具有许多优越性。但之前利用两种聚电解质直接复合制备的胶束亲水性较强，对疏水性药物的负载率不高。
Chen Ying通过质子供体PAA和质子受体HPC之间的氢键作用制备了具有半互穿网络聚合物结构的HPC-PAA粒子，显示出了热敏和pH双重敏感性，并利用奥沙利铂中的铂原子与PAA中羧基之间的复合作用负载了亲水性的抗癌药物奥沙利铂。载药粒子具有抗癌活性高，生物相容性好和制备方法温和的优点。此外，他还通过在碱性条件下将HPC核去除以制得具有对蛋白质药物牛血清白蛋白、抗癌药物盐酸阿霉素具有超高负载量的空核-多孔壳的PAA纳米凝胶，能够保护内部的药物不变性且具有较好的缓释效应。Hu Yong利用两种带相反电荷的聚电解质之间的作用制备了负载阿霉素(DOX)的CS-PAA中空纳米球，与游离的DOX相比显示出长效、低毒的特征，在肝脏中可达较高浓度，且能够输送到脑部，研究表明这是一种制备有着较好的生物相容性和生物降解性的中空聚合物纳米粒子的简单、直接的方法。上述这些研究说明了纳米胶束在基因传递、抗癌类药物释放领域有着巨大的应用潜力。
发明内容
为了既满足胶束提高对疏水性药物的负载率、发挥缓释药物的功能，又能到达容易制备、性能优良、安全易降解的目的，本发明通过DEMA与DAA共聚形成胶束的核，海藻酸中的羧基与PDEMA中的氨基间的静电引力形成胶束的壳，得到核壳型结构的胶束。
海藻酸的制备：采用电动搅拌装置控制较高的搅拌速度，将一定浓度的海藻酸钠溶液缓慢滴入一定浓度的盐酸溶液中，滴加完毕继续搅拌1h，并用玻璃棒挤压沉淀以提高其酸化程度。所得沉淀用去离子水洗涤、过滤至滤液呈中性，再用少量无水乙醇浸泡1h，过滤，真空干燥至恒重。
胶束的制备：取0.5g经过充分干燥、研成粉末的海藻酸和30mL超纯水加入三口瓶中，电动搅拌20min后，加入10mL溶有0.39gDEMA的溶液，电动搅拌20min后，再加入30mL溶有0.21gDAA的溶液，以K2S2O8为引发剂，搅拌均匀的体系在70℃下反应90min得到胶束。
载药胶束的制备：将制备胶束的三种组分混合均匀后，加入一定量的布洛芬，搅拌使其混合均匀，升温至70℃后加入一定量的K2S2O8，反应90min，冷却至室温后用去离子水透析12小时除去未反应的单体及小分子的盐，在10000r/min的转速下离心20min分离出未被包埋的布洛芬，剩余部分加入超纯水重新分散至原体积，得载药胶束。
药物累积释放百分率的测定：精密量取一定量的载药胶束于透析袋内，分别置于一定量的介质为0.01M pH＝5.8、7.4、8.0的磷酸盐缓冲溶液(PBS)中、0.9％、0.6％、0.3％的NaCl溶液、超纯水中，控制水浴温度为37±0.5℃，慢速磁力搅拌，每隔一定时间取样并加入相同体积相同温度的新鲜释放介质。通过紫外分光光度计检测样品中药物的浓度。
结论：控制两种三组分不同的摩尔比，通过透射电子显微镜观察胶束的形貌，纳米粒度仪测量胶束的粒径及其分布，得出当三者的摩尔比为1∶1∶0.5时效果最好，胶束形貌规整、粒径分布最窄，对疏水性药物的负载率最高。药物释放结果表明载药胶束在模拟人体生理条件下具有良好的缓释效果。
本发明的优点：
1、所用原料海藻酸钠的生物相容性好、可生物降解；PDEMA使胶束具有pH敏感性；PDAA可以提高对疏水性药物布洛芬的负载量。
2、制备方法简单、不使用有机溶剂，节能环保，且所得胶束形态规整，大小均匀，稳定性较好。
3、制备胶束的同时可以提高对疏水性药物布洛芬的负载率，且具有良好的缓释效果。
附图说明
图1红外光谱图(a)ALG-H，(b)PDEMA，(c)PDAA，(d)ADD-05
图2荧光光谱图alginate(■)，(b)ADD-05(●)，(c)ADD-025(▲)，(d)ADD-0167
(e)ADD-0125(◆)
图3胶束(ADD-05)的透射电镜照片
图4载药胶束(ADD-0)在pH＝7.4(■)的磷酸盐缓冲溶液(PBS)中；载药胶束(ADD-05)分别在pH＝5.8(●)、7.4(▲)、8.0
的PBS中；载药胶束(ADD-05)分别在超纯水(■)、0.3％(●)、0.6％(▲)、0.9％
的NaCl溶液中的累积释药百分率曲线图
具体实施方式
实施例1
海藻酸的制备：配制1.5％(m/v)的海藻酸钠溶液1000mL，搅拌均匀后静置除气泡；配制5％(m/v)的盐酸溶液2500mL。采用电动搅拌装置控制较高的搅拌速度，将海藻酸钠溶液缓慢滴入盐酸溶液中，滴加完继续搅拌1h，并不断用玻璃棒挤压沉淀以提高其酸化程度。过滤出沉淀，用去离子水洗涤、过滤至滤液呈中性。所得沉淀用少量无水乙醇浸泡1h，过滤，真空干燥至恒重。
实施例2
胶束的制备：取0.5g经过充分干燥、研成粉末的海藻酸和30mL超纯水加入三口瓶中，电动搅拌20min后，加入10mL溶有0.39g DEMA的溶液，电动搅拌20min后，再加入30mL溶有0.21gDAA的溶液，以K2S2O8为引发剂，搅拌均匀的体系在70℃下反应90min得到胶束。
用红外光谱仪、荧光分光光度计对胶束结构进行了表征，如图1、2，红外光谱图1(d)中的胶束在1610cm-1处-COONH中N-H弯曲振动吸收峰明显增强，说明ALG-H中的羧基与PDEMA中的氨基之间通过静电引力结合在了一起，3370cm-1处归属于海藻酸中的-OH和DAA中的N-H伸缩振动吸收峰。胶束的红外光谱中包含了三种组分中的特征吸收峰。
用荧光分光光度计对不同DAA含量的胶束的CMC值进行了表征，结果表明：随着疏水性组分DAA含量的增加，胶束的CMC降低。其中较理想的一组胶束ADD-05其CMC值为0.005mg/ml。用透射电子显微镜对胶束形貌进行了观察，如图3，说明了控制三组分的摩尔比为1∶1∶0.5时，所得胶束尺寸在120nm左右，形态较规整，粒径分布较窄。
实施例3
载药胶束的制备：将制备胶束的三种组分混合均匀后，加入一定量的布洛芬，搅拌使其混合均匀，升温至70℃后加入一定量的K2S2O8，反应90min，冷却至室温后用去离子水透析12小时除去未反应的单体及小分子的盐，在10000r/min的转速下离心20min分离出未被包埋的布洛芬，剩余部分加入超纯水重新分散至原体积，得载药胶束。
实施例4
药物累积释放百分率的测定：精密量取4ml载药胶束(ADD-0)于透析袋内，置于250ml介质为0.01M pH＝7.4的PBS中；精密量取4ml载药胶束(ADD-05)于透析袋内，分别置于250ml介质为0.01M pH＝5.8、7.4、8.0的PBS中；超纯水中，0.3％、0.6％、0.9％的NaCl溶液中，控制水浴温度为37±0.5℃，慢速磁力搅拌，每隔一定时间取样4ml并加入相同体积相同温度的新鲜释放介质，通过紫外分光光度计检测样品中药物的浓度。图4给出所制备的载药胶束在不同条件下的缓释结果。
Claims (5)
1.一种三组分的聚合物胶束，其特征是通过DEMA和DAA共聚形成胶束的核，海藻酸中的羧基与PDEMA中氨基之间的静电引力形成胶束的壳，胶束有pH敏感性。
2.根据权利要求1所述的胶束，其特征是采用“一锅法”制备含有三种聚合物的胶束。聚合物之一是将粘均分子量为2.01×105的海藻酸钠进行酸化处理得到，进行酸化处理过程中海藻酸钠与HCl的摩尔比为1∶45，室温高速搅拌1h，过滤、洗涤至滤液呈中性，无水乙醇浸泡1h后真空干燥得到海藻酸，其酸化程度为90％，聚合物之二三是通过DEMA与DAA在水中聚合得到，其数均分子量为2.40×104。
3.一种权利要求1所述的胶束的制备方法：取0.5g经过充分干燥、研成粉末的海藻酸和30mL超纯水加入三口瓶中，电动搅拌20min后，加入10mL溶有0.39g DEMA的溶液，电动搅拌20min后，再加入30mL溶有0.21gDAA的溶液，以K2S2O8为引发剂，搅拌均匀的体系在70℃下反应90min得到胶束。
4.根据权利要求3所述的胶束，当三种组分者的摩尔比为1∶1∶0.5时，所得胶束形貌最为规整，为近似球形的纳米粒子，平均粒径为120nm左右，粒径分布最窄，对疏水性药物的负载率最高。
5.一种权利要求1所述的载药胶束的制备方法：将制备胶束的三种组分混合均匀后，加入一定量的布洛芬，搅拌使其混合均匀，升温至70℃后加入一定量的K2S2O8，反应90min，冷却至室温后用去离子水透析12小时除去未反应的单体及小分子的盐，在10000r/min的转速下离心20min分离出未被包埋的布洛芬，剩余部分加入超纯水重新分散至原体积，得载药胶束，其特征是制备胶束的同时可以负载疏水性的药物布洛芬，且可以提高负载率。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110335423.5A CN103083222B (zh) | 2011-10-28 | 2011-10-28 | 一锅法制备三组分聚合物胶束 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110335423.5A CN103083222B (zh) | 2011-10-28 | 2011-10-28 | 一锅法制备三组分聚合物胶束 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103083222A true CN103083222A (zh) | 2013-05-08 |
| CN103083222B CN103083222B (zh) | 2015-08-19 |
Family
ID=48196709
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110335423.5A Expired - Fee Related CN103083222B (zh) | 2011-10-28 | 2011-10-28 | 一锅法制备三组分聚合物胶束 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103083222B (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108299597A (zh) * | 2018-01-18 | 2018-07-20 | 嘉兴学院 | 一种合成双丙酮丙烯酰胺与海藻酸钠共聚物的方法 |
| CN110302155A (zh) * | 2019-07-31 | 2019-10-08 | 江南大学 | 一种黄原胶共聚物纳米胶束的制备方法及其应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1612726A (zh) * | 2001-11-13 | 2005-05-04 | 山之内制药技术股份有限公司 | 可溶的药物缓释系统 |
| US20090148384A1 (en) * | 2007-12-10 | 2009-06-11 | Fischer Katrin | Functionalized, solid polymer nanoparticles comprising epothilones |
| CN101503497A (zh) * | 2009-03-02 | 2009-08-12 | 江南大学 | 一种星型嵌段酸敏性纳米胶束的制备方法 |
| US20100196280A1 (en) * | 2006-06-08 | 2010-08-05 | Katrin Claudia Fischer | Functionalized solid polymer nanoparticles for diagnostic and therapeutic applications |
-
2011
- 2011-10-28 CN CN201110335423.5A patent/CN103083222B/zh not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1612726A (zh) * | 2001-11-13 | 2005-05-04 | 山之内制药技术股份有限公司 | 可溶的药物缓释系统 |
| US20100196280A1 (en) * | 2006-06-08 | 2010-08-05 | Katrin Claudia Fischer | Functionalized solid polymer nanoparticles for diagnostic and therapeutic applications |
| US20090148384A1 (en) * | 2007-12-10 | 2009-06-11 | Fischer Katrin | Functionalized, solid polymer nanoparticles comprising epothilones |
| CN101503497A (zh) * | 2009-03-02 | 2009-08-12 | 江南大学 | 一种星型嵌段酸敏性纳米胶束的制备方法 |
Non-Patent Citations (2)
| Title |
|---|
| 王俊峰 等: "双丙酮丙烯酰胺的制备及应用研究进展", 《涂料工业》 * |
| 王晓蕾 等: "pH响应性聚合物胶束及其在抗癌药物给药系统中的研究进展", 《中国新药杂志》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108299597A (zh) * | 2018-01-18 | 2018-07-20 | 嘉兴学院 | 一种合成双丙酮丙烯酰胺与海藻酸钠共聚物的方法 |
| CN110302155A (zh) * | 2019-07-31 | 2019-10-08 | 江南大学 | 一种黄原胶共聚物纳米胶束的制备方法及其应用 |
| WO2021017335A1 (zh) * | 2019-07-31 | 2021-02-04 | 江南大学 | 一种黄原胶共聚物纳米胶束的制备方法及其应用 |
| US11623968B2 (en) | 2019-07-31 | 2023-04-11 | Jiangnan University | Method for preparation of xanthan gum copolymer nanomicelles |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103083222B (zh) | 2015-08-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zavareh et al. | Chitosan/carbon quantum dot/aptamer complex as a potential anticancer drug delivery system towards the release of 5-fluorouracil | |
| Zhang et al. | Intracellular pH-sensitive PEG-block-acetalated-dextrans as efficient drug delivery platforms | |
| Huo et al. | A new class of silica cross-linked micellar core− shell nanoparticles | |
| Talelli et al. | Superparamagnetic iron oxide nanoparticles encapsulated in biodegradable thermosensitive polymeric micelles: toward a targeted nanomedicine suitable for image-guided drug delivery | |
| Li et al. | Amphiphilic chitosan derivative-based core–shell micelles: Synthesis, characterisation and properties for sustained release of Vitamin D3 | |
| Chen et al. | Hollow core− porous shell structure poly (acrylic acid) nanogels with a superhigh capacity of drug loading | |
| CN100563716C (zh) | 生物相容的单分散纳米聚合物载体及其制备和载药方法 | |
| Gao et al. | Injectable shell-crosslinked F127 micelle/hydrogel composites with pH and redox sensitivity for combined release of anticancer drugs | |
| Sun et al. | Benzaldehyde-functionalized polymer vesicles | |
| Muddineti et al. | Curcumin-loaded chitosan–cholesterol micelles: evaluation in monolayers and 3D cancer spheroid model | |
| Deka et al. | Acidic pH-responsive nanogels as smart cargo systems for the simultaneous loading and release of short oligonucleotides and magnetic nanoparticles | |
| Gui et al. | Embedding fluorescent mesoporous silica nanoparticles into biocompatible nanogels for tumor cell imaging and thermo/pH-sensitive in vitro drug release | |
| Zhang et al. | Comparison in docetaxel-loaded nanoparticles based on three different carboxymethyl chitosans | |
| WO2014133172A1 (ja) | 物質内包ベシクル及びその製造方法 | |
| EP2907509A1 (en) | Electrostatic-bonding-type vesicle including metal microparticles | |
| CN104231155A (zh) | 胆固醇修饰两亲性pH响应刷状共聚物和制备及其胶束 | |
| Šachl et al. | Preparation and characterization of self-assembled nanoparticles formed by poly (ethylene oxide)-block-poly (ε-caprolactone) copolymers with long poly (ε-caprolactone) blocks in aqueous solutions | |
| CN112999153B (zh) | 载化疗药物/光敏剂的纳米胶束及其制备方法和应用 | |
| CN105131182B (zh) | 普朗尼克‑聚(β‑氨基酯)聚合物及其合成和应用方法 | |
| Guo et al. | Novel alginate coated hydrophobically modified chitosan polyelectrolyte complex for the delivery of BSA | |
| CN103110954A (zh) | 胆固醇修饰的生物可降解聚阳离子载体及制备方法和用途 | |
| Liang et al. | Folate-functionalized assembly of low density lipoprotein/sodium carboxymethyl cellulose nanoparticles for targeted delivery | |
| Zhong et al. | Galactose-based polymer-containing phenylboronic acid as carriers for insulin delivery | |
| Huang et al. | Therapeutic nanosystems co-deliver anticancer drugs and oncogene SiRNA to achieve synergetic precise cancer chemo-gene therapy | |
| Li et al. | Synthesis and characterization of dendritic star-shaped zwitterionic polymers as novel anticancer drug delivery carriers |
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 | ||
| CB03 | Change of inventor or designer information |
Inventor after: Liu Jie Inventor before: Ni Caihua Inventor before: Cai Hong Inventor before: Zhang Liping |
|
| CB03 | Change of inventor or designer information | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20170920 Address after: The 063000 District of Tangshan City in Hebei province Lutai Province Lu Nan Zhen Xi Shuang Zhuang 3 area 5 ranked No. 2 Patentee after: Liu Jie Address before: School of chemical engineering Jiangnan University No. 1800 214122 Jiangsu city of Wuxi Province Li Lake Avenue Patentee before: Jiangnan University |
|
| TR01 | Transfer of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20150819 Termination date: 20171028 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |