CN112472807B - 一种载药纳米高分子囊泡制备方法 - Google Patents

一种载药纳米高分子囊泡制备方法 Download PDF

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CN112472807B
CN112472807B CN202011415506.0A CN202011415506A CN112472807B CN 112472807 B CN112472807 B CN 112472807B CN 202011415506 A CN202011415506 A CN 202011415506A CN 112472807 B CN112472807 B CN 112472807B
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王生
张鑫璐
程国辉
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Abstract

本发明公开一种载药纳米高分子囊泡及其制备方法,将不饱和脂肪酸两亲性聚合物和光敏剂衍生物金属螯合物通过自组装形成的囊泡状纳米粒子，并在其亲水空腔内包载水溶性化疗药物；其中：光敏剂为2‑((1’‑正己氧基)乙基)‑2‑二乙烯基‑焦脱镁叶绿酸‑a(HPPH)，所述光敏剂衍生物为聚乙二醇‑HPPH键接物。囊泡疏水层的光敏剂分子可在激光照射下高效产生单线态氧，进而氧化高分子链上的不饱和脂肪酸分子，生成亲水性过氧化物基团，实现囊泡通透性变化及结构破坏，快速释放亲水内腔的化疗药物，不饱和脂肪酸过氧化物在催化剂的作用下，又可再次生成活性氧。

Description

一种载药纳米高分子囊泡制备方法
技术领域
本发明属于药物技术领域,涉及一种载药纳米高分子囊泡制备方法。
背景技术
恶性肿瘤是威胁人类生命健康的重大疾病，并且恶性肿瘤的发病率和死亡率逐年提高。化学治疗是利用化学药物杀灭癌细胞的一种全身性治疗手段。随着近年来多种高效抗肿瘤药物的开发与应用，化疗在恶性肿瘤的临床治疗上发挥着重要的作用，但是由于大部分化疗药物选择性差，容易造成全身性分布，因此其在杀灭癌细胞的同时也会损伤人体正常的细胞，从而出现严重的药物副作用。近年来，纳米生物技术的发展为开发新型化疗制剂提供了一个全新的多功能平台，采用纳米技术可将小分子药物制备成纳米药物。与传统剂型相比，纳米药物既可增加药物稳定性，又可通过被动靶向、主动靶向等效应实现对肿瘤的靶向治疗，降低药物的全身性毒副作用并提高生物利用度。基于以上这些优点，纳米药物的开发与应用有望大幅度提高恶性肿瘤的治疗效率而受到广泛研究与关注。
近年来，将光动力治疗作为化疗的辅助治疗手段已受到广泛研究，并获得了比单一疗法更好的治疗效果。并且，采用活性氧敏感的纳米载体同时包载药物和光敏剂，不仅可实现药物的可控释放，还可以通过联合化学药物与活性氧的作用实现更好的治疗效果。然而，仍有一个瓶颈问题有待解决：通过消耗活性氧来实现药物的释放，虽提高了化疗效果，但却以降低活性氧治疗效果为代价，不能实现最优化的联合治疗。尤其是大部分肿瘤组织内氧含量不高，进一步限制了活性氧产量，因此解决上述瓶颈问题具有重要的意义。
发明内容
本发明为克服现有技术的不足，提供一种载药纳米高分子囊泡制备方法。
本发明为解决上述技术问题，提供的技术方案是一种载药纳米高分子囊泡制备方法,将不饱和脂肪酸两亲性聚合物和光敏剂衍生物金属螯合物通过自组装形成的囊泡状纳米粒子，并在其亲水空腔内包载水溶性化疗药物；
其中：光敏剂为2-((1’-正己氧基)乙基)-2-二乙烯基-焦脱镁叶绿酸-a(HPPH)，所述光敏剂衍生物为聚乙二醇-HPPH键接物；
不饱和脂肪酸两亲性聚合物及光敏剂衍生物金属螯合物的结构分别如式(I)、(II)所示：
Figure BDA0002817551750000021
其中：m为1-5的整数；n为1-300的整数；各个X独立地为O或NH；
R1为聚乙二醇单甲醚，分子量为400～10000；
R2为-H、-CH3或-CH2CH3；
R3为亚油酸、花生四烯酸或二十二碳六烯酸；
Z为铁、铜、锰或钴。
所述不饱和脂肪酸两亲性聚合物具有式(III)的优选结构：
Figure BDA0002817551750000022
所述光敏剂衍生物金属螯合物具有式(IV)的优选结构：
Figure BDA0002817551750000023
本发明具体包括如下步骤：
1)将不饱和脂肪酸两亲性聚合物与光敏剂金属螯合物溶于有机溶剂中，形成有机相；
2)将水溶性化疗药物溶于纯水中，形成药物水相；
3)在超声作用下，将药物水相加入到油相中，超声分散；
4)在超声作用下，继续加入纯水，超声形成均匀的乳液分散体系；
5)将上述乳液于旋转蒸发仪上进行旋蒸，至有机溶剂完全挥发，得到包载药物的纳米高分子囊泡。
所述步骤1)中不饱和脂肪酸两亲性聚合物与光敏剂金属螯合物的质量比为1～1000:1，在所得到的有机溶液中，不饱和脂肪酸两亲性聚合物的浓度为0.01mg/mL～100mg/mL。
所述步骤2)中药物的浓度为0.01mg/mL～10mg/mL。
所述步骤2)药物与步骤1)不饱和脂肪酸两亲性聚合物的质量比为1:2～100。
所述步骤3)中水相与油相体积比为1:1～50。
所述步骤4)中新加入水相与油相体积比为1～100:1。
有益效果
本发明涉及的包载药物的纳米高分子囊泡的性能包括：囊泡疏水层的光敏剂分子可在激光照射下高效产生单线态氧，进而氧化高分子链上的不饱和脂肪酸分子，生成亲水性过氧化物基团，实现囊泡通透性变化及结构破坏，快速释放亲水内腔的化疗药物，不饱和脂肪酸过氧化物在催化剂(光敏剂金属螯合物)的作用下，又可再次生成活性氧。
附图说明
图1是实施例1中制备的包载药物的纳米高分子囊泡的透射电镜照片；
图2是实施例1中制备的包载药物的纳米高分子囊泡的粒径表征结果；
图3是实施例1中制备的包载药物的纳米高分子囊泡的紫外吸收光谱。
具体实施方式
以下结合附图对本发明作进一步的说明。
实施例1
称取10mg基于亚油酸的两亲性聚合物、1mg聚乙二醇-HPPH铁离子螯合物溶于4mL二氯甲烷，称取1mg阿霉素盐酸盐溶于0.5mL纯水，将药物水溶液在超声作用下加入到二氯甲烷溶液中，超声分散后继续加入8mL纯水，超声形成均匀的乳液分散体系，于旋转蒸发仪上进行旋蒸，至有机溶剂完全挥发，得到包载药物的纳米高分子囊泡。透射电镜照片如图1所示，粒径表征结果如图2所示，紫外吸收光谱如图3所示。
实施例2
称取8mg基于花生四烯酸的两亲性聚合物、0.5mg聚乙二醇-HPPH铁离子螯合物溶于2mL二氯甲烷，称取0.5mg阿霉素盐酸盐溶于1mL纯水，将药物水溶液在超声作用下加入到二氯甲烷溶液中，超声分散后继续加入5mL纯水，超声形成均匀的乳液分散体系，于旋转蒸发仪上进行旋蒸，至有机溶剂完全挥发，得到包载药物的纳米高分子囊泡。
实施例3
称取8mg基于花生四烯酸的两亲性聚合物、1mg聚乙二醇-HPPH铜离子螯合物溶于4mL三氯甲烷，称取0.8mg表阿霉素盐酸盐溶于1mL纯水，将药物水溶液在超声作用下加入到三氯甲烷溶液中，超声分散后继续加入10mL纯水，超声形成均匀的乳液分散体系，于旋转蒸发仪上进行旋蒸，至有机溶剂完全挥发，得到包载药物的纳米高分子囊泡。
实施例4
称取12mg基于亚油酸的两亲性聚合物、0.8mg聚乙二醇-HPPH铜离子螯合物溶于3mL三氯甲烷，称取1mg表阿霉素盐酸盐溶于2mL纯水，将药物水溶液在超声作用下加入到三氯甲烷溶液中，超声分散后继续加入6mL纯水，超声形成均匀的乳液分散体系，于旋转蒸发仪上进行旋蒸，至有机溶剂完全挥发，得到包载药物的纳米高分子囊泡。
实施例5
称取10mg基于二十二碳六烯酸的两亲性聚合物、0.6mg聚乙二醇-HPPH铁离子螯合物溶于8mL二氯甲烷，称取1mg伊立替康溶于3mL纯水，将药物水溶液在超声作用下加入到二氯甲烷溶液中，超声分散后继续加入20mL纯水，超声形成均匀的乳液分散体系，于旋转蒸发仪上进行旋蒸，至有机溶剂完全挥发，得到包载药物的纳米高分子囊泡。
实施例6
称取20mg基于花生四烯酸的两亲性聚合物、1mg聚乙二醇-HPPH铁离子螯合物溶于10mL二氯甲烷，称取1.8mg伊立替康溶于4mL纯水，将药物水溶液在超声作用下加入到二氯甲烷溶液中，超声分散后继续加入40mL纯水，超声形成均匀的乳液分散体系，于旋转蒸发仪上进行旋蒸，至有机溶剂完全挥发，得到包载药物的纳米高分子囊泡。
实施例7
称取18mg基于亚油酸的两亲性聚合物、1.8mg聚乙二醇-HPPH铜离子螯合物溶于6mL三氯甲烷，称取1mg伊立替康溶于2mL纯水，将药物水溶液在超声作用下加入到三氯甲烷溶液中，超声分散后继续加入10mL纯水，超声形成均匀的乳液分散体系，于旋转蒸发仪上进行旋蒸，至有机溶剂完全挥发，得到包载药物的纳米高分子囊泡。

Claims (9)

1.一种载药纳米高分子囊泡制备方法,其特征在于，将不饱和脂肪酸两亲性聚合物和光敏剂衍生物金属螯合物通过自组装形成的囊泡状纳米粒子，并在其亲水空腔内包载水溶性化疗药物；
其中：光敏剂为2-((1’-正己氧基)乙基)-2-二乙烯基-焦脱镁叶绿酸-a(HPPH)，所述光敏剂衍生物为聚乙二醇-HPPH键接物；
不饱和脂肪酸两亲性聚合物及光敏剂衍生物金属螯合物的结构分别如式(I)、(II)所示：
Figure FDA0003954400140000011
其中：m为1-5的整数；n为1-300的整数；各个X独立地为O或NH；
R1为聚乙二醇单甲醚，分子量为400～10000；
R2为-H、-CH3或-CH2CH3；
R3为亚油酸、花生四烯酸或二十二碳六烯酸；
Z为铁、铜、锰或钴。
2.根据权利要求1所述的一种载药纳米高分子囊泡制备方法,其特征在于，所述不饱和脂肪酸两亲性聚合物具有式(III)的结构：
Figure FDA0003954400140000012
3.根据权利要求1所述的一种载药纳米高分子囊泡制备方法,其特征在于，所述光敏剂衍生物金属螯合物具有式(IV)的结构：
Figure FDA0003954400140000021
4.根据权利要求1所述的一种载药纳米高分子囊泡制备方法,其特征在于，包括如下步骤：
1)将不饱和脂肪酸两亲性聚合物与光敏剂衍生物金属螯合物溶于有机溶剂中，形成油相；
2)将水溶性化疗药物溶于纯水中，形成药物水相；
3)在超声作用下，将药物水相加入到油相中，超声分散；
4)在超声作用下，继续加入纯水，超声形成均匀的乳液分散体系；
5)将上述乳液于旋转蒸发仪上进行旋蒸，至有机溶剂完全挥发，得到包载药物的纳米高分子囊泡。
5.根据权利要求4所述的一种载药纳米高分子囊泡制备方法,其特征在于，所述步骤1)中不饱和脂肪酸两亲性聚合物与光敏剂衍生物金属螯合物的质量比为1～1000:1，在所得到的有机溶液中，不饱和脂肪酸两亲性聚合物的浓度为0.01mg/mL～100mg/m L。
6.根据权利要求4所述的一种载药纳米高分子囊泡制备方法,其特征在于，所述步骤2)中药物的浓度为0.01mg/mL～10mg/mL。
7.根据权利要求4所述的一种载药纳米高分子囊泡制备方法,其特征在于，所述步骤2)药物与步骤1)不饱和脂肪酸两亲性聚合物的质量比为1:2～100。
8.根据权利要求4所述的一种载药纳米高分子囊泡制备方法,其特征在于，所述步骤3)中水相与油相体积比为1:1～50。
9.根据权利要求4所述的一种载药纳米高分子囊泡制备方法,其特征在于，所述步骤4)中新加入水相与油相体积比为1～100:1。
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Title
不同价态锰对神经母细胞瘤细胞的氧化损伤作用;宣登峰 等;《工业卫生与职业病》;20040730;第30卷(第4期);第222页 *
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