中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (8): 1410-1413.doi: 10.3969/j.issn.1673-8225.2010.08.019

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

溶剂挥发法制备磷脂-聚乳酸纳米粒子及其性质

曹  俊,陈元维,陈年操,罗祥林   

  1. 四川大学高分子科学与工程学院,四川省成都市  610065
  • 出版日期:2010-02-19 发布日期:2010-02-19
  • 通讯作者: 罗祥林,教授,博士后,博士生导师,四川大学高分子科学与工程学院医用高分子与人工器官系,四川省成都市 610065 luoxl_scu@126.com
  • 作者简介:曹 俊★,女,1986年生,四川省内江市人,汉族,四川大学高分子科学与工程学院在读硕士,主要从事生物材料的研究。 caojun198610301981@126.com
  • 基金资助:

    国家自然科学基金资助项目(50473065);国际科技合作资助项目(2006DFA53470).

Self-assembly preparation of phosphorylcholine-containing poly (L-lactide) nanoparticles with solvent evaporation method and its characteristics

Cao Jun, Chen Yuan-wei, Chen Nian-cao, Luo Xiang-lin   

  1. College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, Sichuan Province, China
  • Online:2010-02-19 Published:2010-02-19
  • Contact: Luo Xiang-lin, Professor, Doctor, Doctoral supervisor, Department of Polymer Science and Engineering, Sichuan University, Chengdu 610065, Sichuan Province, China luoxl_scu@126.com
  • About author:Luo Xiang-lin, Professor, Doctor, Doctoral supervisor, Department of Polymer Science and Engineering, Sichuan University, Chengdu 610065, Sichuan Province, China luoxl_scu@126.com
  • Supported by:

    the National Natural Science Foundation of China, No. 50473065*; International Science & Technology Cooperation, No.2006DFA53470*

摘要:

背景:含磷脂胆碱的聚乳酸具有优良的生物相容性和降解性能,而且是两性分子。课题前期研究表明用成膜水化法可以自组装成胶束来作为药物载体,但随着疏水链段的增加,成膜水化法很难形成胶束,对于疏水链段较长的磷脂胆碱聚合物能否形成胶束来作为药物载体,目前尚不清楚。
目的:采用溶剂挥发法制备磷脂胆碱聚乳酸[phosphorylcholine-containing poly (L-lactide),PLLA-PC]自组装纳米粒子,探讨影响纳米粒子形成和稳定性的因素。
方法: ①制备PLLA-PC纳米粒子:将PLLA-PC的丙酮溶液滴加到二蒸水中,在室温下磁力搅拌至丙酮挥发完全。F-7000FL220-240V荧光/磷光分光光度计测试胶束溶液的临界胶束浓度,芘为荧光探针,发射波长为395 nm,激发波长为300 nm。JEM-100CX透射电子显微镜观察纳米粒子形态;NANOZSZEN 3600纳米粒度分析仪测其粒径及粒径分布,测试温度为25 ℃。②凝胶渗透色谱仪GPC测定相对分子质量,色谱仪为Waters 717,流动相为THF,流速1.0 mL/min,聚苯乙烯为标样。每次进样时注入50 μL质量浓度为1 g/L样品溶液。
结果与结论:透射电镜显示,PLLA-PC自组装纳米粒子呈壳/核结构。荧光探针检测临界胶束浓度表明,PLLA-PC有很强的表面活性,临界胶束浓度均低于10-3 g/L,且随LLA比例变化。动态光散射结果表明,聚合物的亲/疏水链段比例、有机溶剂以及水的用量在纳米粒子形成过程中对粒径有影响,纳米粒子用水稀释时粒径变化不大,且37 ℃可发生降解。提示溶剂挥发法可以制备粒径可控的PLLA-PC纳米粒子,有望用作新型的纳米药物载体。

关键词: 磷脂胆碱聚乳酸, 自组装, 纳米粒子, 溶剂挥发法, 纳米生物材料

Abstract:

BACKGROUND: Phosphorylcholine-containing poly (L-lactide) (PLLA-PC) is a kind of novel amphiphilic copolymer with good biocompatibility and biodegradability. In the previous work, self-assembly micelles of PLLA-PC were prepared with film rehydration method. But it hardly formed micelle with film rehydration method because the longer chains of LLA existed in the PLLA-PC copolymer. However, the mechanism of phospholipid choline polymer with long hydrophobic chain forming micelle remains still unclear.
OBJECTIVE: To prepare self-assembling nanoparticles of PLLA-PC using solvent evaporation method, and to explore the factors that affected the properties and stability of nanoparticles.
METHODS:  ① Nanoparticles were prepared with solvent evaporation method.  PLLA-PC copolymer was dissolved into acetone, and the copolymer solution was added dropwise to distilled water with stirring to yield nanoparticles. The critical micelle concentration (CMC) was performed on the F-7000FL220-240V. The emission and excitation wavelength were 395 nm and 300 mm, respectively. Transmission electron microscopy (TEM) was carried out on a JEM-100CX electron microscope to observe the morphology of PLLA-PC nanoparticles. Dynamic light scattering measurements on nanoparticle solutions were performed on a NANOSIZE 3600 at room temperature. ② Gel permeation chromatography (GPC) measurements were performed on a Waters 717 apparatus equipped with an RI detector. THF was used as the mobile phase at a flow rate of 1.0 mL/min. A 1 g/L solution   (50 μL) was injected for each analysis.
RESULTS AND CONCLUSION: TEM indicated that the PLLA-PC nanoparticles presented typical shell/core structure. The critical micelle concentration was determined by fluorescent probe method. The results showed that the CMCs were quite low (< 10-3 g/L) and were dependent on the LLA units in the copolymer. The size and size distribution of the nanoparticles were detected by dynamic light scattering. The results indicated that the size could be affected by the LLA units, concentration of the organic solution and the concentration of the aqueous solution of the nanoparticles. On the other hand, they hardly changed over the dilution with water, which was of great importance in venous injection. They degraded at 37 ℃. PLLA-PC nanoparticles with controllable sizes can be prepared with phase separation method and might serve as a novel material for drug delivery.

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