CN108635590B - 一种pH响应的多糖–硼替佐米纳米球及其制备方法和应用 - Google Patents
一种pH响应的多糖–硼替佐米纳米球及其制备方法和应用 Download PDFInfo
- Publication number
- CN108635590B CN108635590B CN201810926034.1A CN201810926034A CN108635590B CN 108635590 B CN108635590 B CN 108635590B CN 201810926034 A CN201810926034 A CN 201810926034A CN 108635590 B CN108635590 B CN 108635590B
- Authority
- CN
- China
- Prior art keywords
- solution
- bortezomib
- nanosphere
- hyaluronic acid
- glucose
- 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.)
- Active
Links
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
- A61K47/56—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
- A61K47/61—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 the organic macromolecular compound being a polysaccharide or a derivative thereof
-
- 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
- A61K31/69—Boron compounds
-
- 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
- A61K47/6921—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 a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—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 a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
- A61K47/6929—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 a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
- A61K47/6931—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 a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
- A61K47/6939—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 a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nanotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
一种pH响应的多糖–硼替佐米纳米球及其制备方法和应用。所述纳米球构筑单元为葡萄糖修饰透明质酸和抗癌药物硼替佐米,通过药物分子上的硼酸基团和葡萄糖顺式二醇之间的硼酸酯键作用交联,形成以亲水的透明质酸为外壳、疏水的硼替佐米为内核的纳米球,纳米球粒径为100‑120nm,并对pH具有很好的药物释放响应性。本发明的优点是:透明质酸是一类亲生物的靶向聚多糖分子,能够将药物靶向的运输到癌细胞内,减少对正常组织的毒副作用;硼酸基团能够与葡萄糖的顺式二醇形成pH响应的硼酸酯键,实现药物的刺激响应性释放;该pH响应的纳米球制备方法简单、易于实施且原料成本低,使其在癌症的靶向治疗领域具有广阔的应用前景。
Description
【技术领域】
本发明涉及抗癌药物靶向传递技术领域,特别是一种pH响应的多糖–硼替佐米纳米球及其制备方法和应用。
【背景技术】
癌症已经成为世界各国面临的最严峻的社会问题之一,严重的危害人类的健康和生活,并且它的发病率正在逐年上升。目前,化学药物治疗由于其高效性是临床上治疗癌症最有效的手段。然而,其仍然面临着水溶性差、缺少靶向性、生物利用度低、耐药性以及对正常组织的毒副作用等严重问题,极大的影响了治疗效果。因此,为了克服上述问题,将癌细胞靶向特异性配体与具有刺激响应性能的构建块结合起来构筑具有刺激响应性的靶向药物传递体系在近几年得到了极为快速的发展,并在药物治疗中具有以下几个优势:1)通过修饰靶向配体,抗癌药物能够区分肿瘤细胞和正常细胞,进而可以增强抗癌药物在肿瘤组织内的累积,降低对正常组织的毒副作用;2)将抗癌药物与水溶性载体结合,能够增加药物的水溶性和生物相容性;3)可以利用癌细胞自身环境内的变化如pH、氧化还原电位、酶等作为药物释放的刺激剂。常见的构筑刺激响应性的靶向药物传递体系的方法是通过共价键进行连接,然而这个过程需要复杂的合成和分离,费时费力。动态共价键不仅可以避免复杂的合成和提纯过程,而且可以方便快捷地引入不同种类的功能基团实现体系的多功能化。因此,将动态共价键应用到药物传递体系的构建上具有很好的应用前景。
【发明内容】
本发明的目的是针对上述技术分析和存在问题,提供一种pH响应的多糖–硼替佐米纳米球及其制备方法和应用。
众所周知,硼酸能够可逆的键合顺式二醇生成稳定的硼酸酯键这种动态共价键,由于其对pH值的快速响应性,硼酸酯键被用作刺激响应性药物传递体系的构筑模块。透明质酸是一类具有很好水溶性和生物相容性的聚多糖分子,能够靶向识别癌细胞表面过量表达的透明质酸受体如透明质酸结合蛋白CD44以及RHAMM,进而能够将药物传递到癌细胞内。因此,将硼酸酯键和透明质酸相结合运用到抗癌药物的传输体系中,不仅可以改善药物的水溶性和生物相容性,而且可以赋予其靶向和刺激响应释放功能。该纳米球以葡萄糖修饰透明质酸(HAGlu)和抗癌药物硼替佐米(BTZ)为构筑单元,利用硼酸和葡萄糖顺式二醇之间的硼酸酯键作用构筑以亲水的透明质酸为外壳、疏水的硼替佐米为内核的纳米球,由于硼酸酯键对pH的响应性,在中性pH条件下纳米球稳定存在,在酸性条件下硼酸酯键断开,抗癌药物硼替佐米被释放出来;该纳米球制备方法简单,对癌细胞的选择性和杀伤作用强,毒副作用低,适于放大合成和实际生产应用。
本发明的技术方案:
一种pH响应的多糖–硼替佐米纳米球,其构筑单元为葡萄糖修饰透明质酸和抗癌药物硼替佐米,通过药物分子上的硼酸基团和葡萄糖顺式二醇之间的硼酸酯键作用交联,形成以亲水的透明质酸为外壳、疏水的硼替佐米为内核的纳米球,纳米球粒径为100-120nm,并对pH具有很好的药物释放响应性。其中葡萄糖修饰透明质酸平均每4.9个透明质酸单元修饰有一个葡萄糖单元,硼替佐米的分子式为C19H25BN4O4,该纳米球构筑单元的结构以及它们之间的硼酸酯键作用示意如下:
一种所述pH响应的多糖–硼替佐米纳米球的制备方法,包括以下步骤:
1)在氮气氛围下,将葡萄糖内酯加入到乙二胺溶液中,在室温下搅拌24h后,将反应液减压蒸馏除去过量的乙二胺,然后在60℃条件下真空干燥24h,得白色固体产物N-(2-氨乙基)-1-葡萄糖酰胺。
2)将分子量为550kDa的透明质酸溶于二甲基亚砜溶液中,在60℃条件下搅拌至透明质酸完全溶解,然后将溶液冷却至室温。向溶液中加入三乙胺,将混合液在室温下搅拌10min后,加入氯甲酸乙酯,再在室温下搅拌1h。然后向混合液中加入步骤1)得到的N-(2-氨乙基)-1-葡萄糖酰胺,继续在室温下搅拌24h。然后将所得溶液装入截留分子量范围为8-14kDa的透析袋中用过量的蒸馏水连续透析5天,将所得溶液冻干制得葡萄糖修饰透明质酸;
3)将上述步骤2)制得的葡萄糖修饰透明质酸溶于水中得到溶液a,将抗癌药物硼替佐米溶于二甲基亚砜中得到溶液b,然后将溶液a和溶液b混合并在室温下搅拌24h后,将所得溶液装入截留分子量范围为8-14kDa的透析袋中用过量的蒸馏水透析1h,将所得溶液冻干制得pH响应的多糖–硼替佐米纳米球。
所述步骤1)葡萄糖内酯与乙二胺溶液的用量比为0.255mol/L。
所述步骤2)透明质酸与二甲基亚砜溶液的用量比为0.026mol/L,三乙胺、氯甲酸乙酯和二甲基亚砜溶液的体积比为0.92:0.377:50,透明质酸与N-(2-氨乙基)-1-葡萄糖酰胺的摩尔比为2:1。
所述步骤3)中溶液a中葡萄糖修饰透明质酸与水的用量比为4.94mmol/L,溶液b中硼替佐米与二甲基亚砜的用量比为1mmol/L,溶液a与溶液b的体积比为25:1。
本发明所述pH响应的多糖–硼替佐米纳米球可应用于癌症药物靶向运输领域。
本发明的优点和有益效果是:1)透明质酸是一类具有很好水溶性和生物相容性的靶向聚多糖分子,能够通过与癌细胞表面过量表达的透明质酸受体间强的抗原–抗体作用,将抗癌药物硼替佐米靶向的运输到癌细胞内,减少对正常组织的毒副作用;2)硼酸是一种pH响应性的分子,它能够与葡萄糖的顺式二醇形成环酯,实现抗癌药物硼替佐米的刺激响应性释放;3)该pH响应的纳米球制备方法简单、易于实施且原料成本低,使其在癌症的靶向治疗领域具有广阔的应用前景。
【附图说明】
图1为pH响应的多糖–硼替佐米纳米球的合成路线示意图。
图2为pH响应的多糖–硼替佐米纳米球的透射电子显微镜图。
图3为硼替佐米释放随pH的变化图。
图4为PC-3细胞的细胞毒性结果。
图5为NIH3T3细胞的细胞毒性结果。
【具体实施方式】
下面通过实例对本发明做进一步的说明:
实施例:
一种pH响应的多糖–硼替佐米纳米球,其构筑单元为葡萄糖修饰透明质酸和抗癌药物硼替佐米,通过药物分子上的硼酸基团和葡萄糖顺式二醇之间的硼酸酯键作用交联,形成以亲水的透明质酸为外壳、疏水的硼替佐米为内核的纳米球,纳米球粒径为100-120nm,并对pH具有很好的药物释放响应性。其中葡萄糖修饰透明质酸平均每4.9个透明质酸单元修饰有一个葡萄糖单元,硼替佐米的分子式为C19H25BN4O4,该纳米球构筑单元的结构以及它们之间的硼酸酯键作用示意如下:
本发明所述pH响应的多糖–硼替佐米纳米球的制备方法,包括以下步骤:
1)在氮气氛围下,将1g(5.61mmol)葡萄糖内酯加入到22mL乙二胺溶液中,在室温下搅拌24h后,将反应液减压蒸馏除去过量的乙二胺,然后在60℃条件下真空干燥24h,得白色固体产物N-(2-氨乙基)-1-葡萄糖酰胺;
检测显示制备的N-(2-氨乙基)-1-葡萄糖酰胺核磁表征如下:1HNMR(400MHz,D2O,TMS,ppm):δ=3.39(s,2H),3.61–3.79(m,6H),4.06(s,1H),4.27(d,1H)。
2)将500mg(1.32mmol)分子量为550kDa的透明质酸溶于50mL二甲基亚砜溶液中,在60℃条件下搅拌至透明质酸完全溶解,然后将溶液冷却至室温。向溶液中加入0.92mL三乙胺,将混合液在室温下搅拌10min后,加入0.377mL氯甲酸乙酯,再在室温下搅拌1h。然后向混合液中加入157mg(0.66mmol)N-(2-氨乙基)-1-葡萄糖酰胺,继续在室温下搅拌24h。然后将所得溶液装入截留分子量范围为8-14kDa的透析袋中用过量的蒸馏水连续透析5天,将所得溶液冻干制得葡萄糖修饰透明质酸;
检测显示制备的葡萄糖修饰透明质酸核磁表征如下:1H NMR(400MHz,D2O,TMS,ppm):δ=2.0(s,3H),3.16–3.21(q,0.81H),3.35–4.13(m,12.96H),4.45–4.54(m,2H)。葡萄糖的修饰度根据透明质酸骨架上与酰胺基相连的甲基上的三个氢(δ=2.0,3H)和葡萄糖乙二胺上亚甲基上的氢(δ=3.16–3.21,4H)的核磁积分面积比计算得到为20.25%,即平均每4.9个透明质酸单元修饰有一个葡萄糖单元。
3)将10.46mg葡萄糖修饰透明质酸溶于5mL水中得到溶液a,将1.92mg抗癌药物硼替佐米溶于200μL二甲基亚砜中得到溶液b,然后将溶液a和溶液b混合并在室温下搅拌24h后,将所得溶液装入截留分子量范围为8-14kDa的透析袋中用过量的蒸馏水透析1h,将所得溶液冻干制得pH响应的多糖–硼替佐米纳米球。
图1为pH响应的多糖–硼替佐米纳米球的合成路线示意图。
图2为pH响应的多糖–硼替佐米纳米球的透射电子显微镜图,通过透射电子显微镜表征可以得出该纳米球通过药物分子上的硼酸基团和葡萄糖顺式二醇之间的硼酸酯键作用交联,形成以亲水的透明质酸为外壳、疏水的硼替佐米为内核的纳米球,纳米球粒径为100-120nm。
该纳米球里硼替佐米释放随pH变化的实验验证:
将5mg制备好的纳米球溶于10mL磷酸缓冲溶液中(pH=7.4,I=0.01M),分别取2.5mL溶液将其放入截留分子量为8-14kDa的透析袋中,然后分别在装有40mLpH=5.0,6.5和7.2(I=0.01M)的PBS缓冲溶液中透析,温度控制在37℃。在0.5–12h的时间间隔,取出2.5mL的透析液,然后加入等体积的新鲜溶液。通过紫外测定BTZ在270nm处的吸收进而计算药物在不同pH条件下的累积释放量。图3为硼替佐米释放随pH的变化图。图中表明:在pH=7.2时,有14.3%的硼替佐米从纳米球里面释放出来。随着pH值减小,硼替佐米的释放量增加,在pH 6.5和5.7的情况下,硼替佐米的累计释放量分别为35.1%和57.9%。pH 5.7的释放量是pH 7.2的4倍,说明纳米球具有pH响应的药物释放能力。
本发明的具体应用效果如下:
将PC-3细胞(人前列腺癌细胞)和NIH3T3(小鼠胚胎成纤维细胞)铺在含有10%胎牛血清的DMEM培养基的96孔板中培养24小时,分别加入葡萄糖修饰透明质酸(HAGlu)、硼替佐米(BTZ)、纳米球(HAGlu-BTZ),含有过量透明质酸的纳米球(HAGlu-BTZ+HA),连续培养24小时,用MTT法测量各个实验条件下的细胞生存率。
图4为PC-3细胞的细胞毒性结果,图中表明:在24h范围内HAGlu-BTZ纳米球展现出了比硼替佐米更低的对PC-3肿瘤细胞的抑制作用,当加入过量的透明质酸将细胞表面的透明质酸受体饱和后,纳米球对PC-3细胞的抑制作用减弱,表明这种抑制作用是以细胞受体为媒介的内吞作用将纳米球带入到癌细胞中。对于NIH3T3细胞,如图5所示,BTZ对其具有很大的杀伤作用,然而由于正常细胞表面透明质酸受体的表达远远小于癌细胞,因此HAGlu-BTZ纳米球对正常细胞的毒性比单纯的药物BTZ小很多,从而实现在保护正常细胞的情况下对癌细胞选择性杀伤的目的。
Claims (2)
1.一种pH响应的多糖–硼替佐米纳米球,其特征在于,构筑单元为葡萄糖修饰透明质酸和抗癌药物硼替佐米,通过药物分子上的硼酸基团和葡萄糖顺式二醇之间的硼酸酯键作用交联,形成以亲水的透明质酸为外壳、疏水的硼替佐米为内核的纳米球,纳米球粒径为100-120nm;其中葡萄糖修饰透明质酸平均每4.9个透明质酸单元修饰有一个葡萄糖单元,硼替佐米的分子式为C19H25BN4O4,该纳米球构筑单元的结构以及它们之间的硼酸酯键作用示意如下:
所述pH响应的多糖–硼替佐米纳米球的制备方法包括以下步骤:
1)在氮气氛围下,将葡萄糖内酯加入到乙二胺溶液中,葡萄糖内酯与乙二胺溶液的用量比为0.255mol/L,在室温下搅拌24h后,将反应液减压蒸馏除去过量的乙二胺,然后在60℃条件下真空干燥24h,得白色固体产物N-(2-氨乙基)-1-葡萄糖酰胺;
2)将分子量为550kDa的透明质酸溶于二甲基亚砜溶液中,在60℃条件下搅拌至透明质酸完全溶解,然后将溶液冷却至室温,向溶液中加入三乙胺,将混合液在室温下搅拌10min后,加入氯甲酸乙酯,再在室温下搅拌1h;然后向混合液中加入步骤1)得到的N-(2-氨乙基)-1-葡萄糖酰胺,继续在室温下搅拌24h;然后将所得溶液装入截留分子量范围为8-14kDa的透析袋中用过量的蒸馏水连续透析5天,将所得溶液冻干制得葡萄糖修饰透明质酸;
3)将上述制得的葡萄糖修饰透明质酸溶于水中得到溶液a,将抗癌药物硼替佐米溶于二甲基亚砜中得到溶液b,然后将溶液a和溶液b混合并在室温下搅拌24h后,将所得溶液装入截留分子量范围为8-14kDa的透析袋中用过量的蒸馏水透析1h,将所得溶液冻干制得pH响应的多糖–硼替佐米纳米球;
所述步骤2)透明质酸与二甲基亚砜溶液的用量比为0.026mol/L,三乙胺、氯甲酸乙酯和二甲基亚砜溶液的体积比为0.92:0.377:50,透明质酸与N-(2-氨乙基)-1-葡萄糖酰胺的摩尔比为2:1;
所述步骤3)中溶液a中葡萄糖修饰透明质酸与磷酸缓冲溶液的用量比为4.94mmol/L,溶液b中硼替佐米与二甲基亚砜的用量比为1mmol/L,溶液a与溶液b的体积比为25:1。
2.权利要求1所述pH响应的多糖–硼替佐米纳米球在制备靶向治疗癌症药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810926034.1A CN108635590B (zh) | 2018-08-15 | 2018-08-15 | 一种pH响应的多糖–硼替佐米纳米球及其制备方法和应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201810926034.1A CN108635590B (zh) | 2018-08-15 | 2018-08-15 | 一种pH响应的多糖–硼替佐米纳米球及其制备方法和应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN108635590A CN108635590A (zh) | 2018-10-12 |
CN108635590B true CN108635590B (zh) | 2021-05-18 |
Family
ID=63760881
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201810926034.1A Active CN108635590B (zh) | 2018-08-15 | 2018-08-15 | 一种pH响应的多糖–硼替佐米纳米球及其制备方法和应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN108635590B (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109589402B (zh) * | 2019-01-18 | 2022-03-18 | 山东大学 | 一种具有靶向光热治疗和可控释药的多重作用纳米材料的制备方法及应用 |
CN110368316B (zh) * | 2019-08-14 | 2022-04-22 | 桂林理工大学 | 一种负载有疏水性植物多酚的桃胶多糖纳米球的制备方法 |
CN114686375A (zh) * | 2020-12-30 | 2022-07-01 | 华熙生物科技股份有限公司 | 一种用于培养细胞聚集体的多孔板及其制备和使用方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104958768A (zh) * | 2015-07-17 | 2015-10-07 | 中国科学院长春应用化学研究所 | 一种葡聚糖-硼替佐米键合药及其制备方法 |
CN107660210A (zh) * | 2015-04-29 | 2018-02-02 | 纳米装置有限责任公司 | 基于硼替佐米的递送系统 |
-
2018
- 2018-08-15 CN CN201810926034.1A patent/CN108635590B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN107660210A (zh) * | 2015-04-29 | 2018-02-02 | 纳米装置有限责任公司 | 基于硼替佐米的递送系统 |
CN104958768A (zh) * | 2015-07-17 | 2015-10-07 | 中国科学院长春应用化学研究所 | 一种葡聚糖-硼替佐米键合药及其制备方法 |
Non-Patent Citations (4)
Title |
---|
《Boronate-crosslinked polysaccharide conjugates for pH-responsive and targeted drug delivery》;Yuhui Zhang et al.;《Chemical Communications》;20190103(第55期);1164-1167 * |
pH响应型透明质酸_棉酚纳米粒子的制备及其性能研究;施瑜;《食品与生物技术学报》;20170430;第36卷(第4期);第400页摘要、第402页右栏最后一段 * |
pH敏感性透明质酸纳米凝胶作为药物传递系统的研究;栾淑娟;《中国优秀硕士学位论文全文数据库 医药卫生科技辑》;20180615(第6期);第63页第1段-第64页第4段、第65页3.2.6部分、第65-66页 3.2.7部分和3.2.8部分、第71页第1段、第72页表3-4 * |
Synthesis of Functional Chelating Diphosphines Containing the Bis[2-(diphenylphosphino)ethyl]amino Moiety and the Use of These Materials in the Preparation of Water-Soluble Diphosphine Complexes of Transition Metals;Ralph G et al.;《J.Org.Chem》;19810701;第46卷(第14期);第2866页左栏倒数第1段 * |
Also Published As
Publication number | Publication date |
---|---|
CN108635590A (zh) | 2018-10-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105056213B (zh) | 一种葡萄糖响应的超分子纳米球及其制备方法和应用 | |
CN108635590B (zh) | 一种pH响应的多糖–硼替佐米纳米球及其制备方法和应用 | |
CN103920160B (zh) | 环糊精为媒介的石墨烯/透明质酸组装体及其制备方法 | |
CN102260356B (zh) | 一种用作基因载体的壳聚糖衍生物及其制备方法和用途 | |
Wang et al. | A charge-conversional intracellular-activated polymeric prodrug for tumor therapy | |
Roos et al. | Physicochemical and antitumor characteristics of some polyamino acid prodrugs of mitomycin C | |
CN102863627A (zh) | 顺铂配合物及其制备方法 | |
CN107537039B (zh) | 靶向木质素基纳米载药粒子 | |
Liang et al. | Novel polymeric micelles with cinnamic acid as lipophilic moiety for 9-Nitro-20 (S)-camptothecin delivery | |
CN104127882B (zh) | 一种靶向传递紫杉醇抗癌前药的超分子组装体及制备方法 | |
Lu et al. | Targeted acid-labile conjugates of norcantharidin for cancer chemotherapy | |
CN110732027A (zh) | 一种刺激响应的靶向聚多糖超分子诊疗组装体及其制备方法 | |
CN111249469B (zh) | 一种能够溶酶体逃逸的肽纳米颗粒及其制备方法和应用 | |
CN109306058A (zh) | 一种叶酸和三苯基膦共同修饰的普朗尼克共聚物及其制备方法和用途 | |
CN106727323B (zh) | 一种透明质酸纳米囊泡及其制备方法和应用 | |
JP2022550901A (ja) | 核酸治療薬のための腫瘍標的化ポリペプチドナノ粒子送達システム | |
CN109675048B (zh) | 一种抗癌前药脂质体及青蒿素类脂质体纳米药物 | |
AU2020104042A4 (en) | Preparation Method and Application of PH-responsive Polysaccharide-bortezomib Nanosphere | |
CN103877577B (zh) | 一种肿瘤靶向锌基金属-有机骨架药物载体及其制备方法 | |
CN103055321A (zh) | 一种聚乙二醇单甲醚-聚磷酸酯两嵌段共聚物及其阿霉素键合药 | |
Zhao et al. | Synthesis of zwitterionic chimeric polymersomes for efficient protein loading and intracellular delivery | |
CN115969992A (zh) | 一种用于重塑肿瘤免疫微环境的苯硼酸共聚物及其应用 | |
CN115926134A (zh) | 一种阳离子聚酯及其制备方法和应用 | |
CN104892807A (zh) | 一种表面糖修饰聚合物胶束及其制备方法和应用 | |
US20230181747A1 (en) | Drug loaded peptide brush polymers |
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 | ||
CB03 | Change of inventor or designer information | ||
CB03 | Change of inventor or designer information |
Inventor after: Zhang Yuhui Inventor after: Guo Zeyu Inventor after: Wang Jie Inventor after: Sheng Xianliang Inventor after: Wang Kebing Inventor before: Zhang Yuhui Inventor before: Wang Jie Inventor before: Sheng Xianliang Inventor before: Wang Kebing |
|
GR01 | Patent grant | ||
GR01 | Patent grant |