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聚(环氧乙烷)-聚(环氧丙烷)-聚(环氧乙烷)三嵌段共聚物对脂质体二油酰磷脂酰乙醇胺结构和稳定性的影响

Effects of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers on structure and stability of liposomal dioleoylphosphatidylethanolamine.

作者信息

Bergstrand Nill, Edwards Katarina

机构信息

Department of Physical Chemistry, Uppsala University, Box 579, S-751 23 Uppsala, Sweden.

出版信息

J Colloid Interface Sci. 2004 Aug 15;276(2):400-7. doi: 10.1016/j.jcis.2004.03.013.

Abstract

The effects caused by poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO; Pluronic) copolymers on the structure and stability of dioleoylphosphatidylethanolamine (DOPE) liposomes were studied by means of turbidity, leakage, and cryo-transmission electron microscopy investigations. The results show that by inclusion of Pluronics in the DOPE dispersion it is possible to stabilize the lamellar Lalpha phase and to produce liposomes that are stable and nonleaky at low pH (pH 5). The stabilizing capacity was observed to depend critically on the molecular composition of the Pluronics. Block copolymers with comparably long PPO and PEO segment lengths, such as F127 and F108, most effectively protected DOPE liposomes prepared at high pH from aggregation and subsequent structural rearrangements induced by acidification. A sufficiently long PPO block was found to be the most decisive parameter in order to obtain adequate coverage of the liposome surface at low Pluronic concentrations. Upon increasing the copolymer concentration, however, Pluronics with comparably short PPO and PEO segment lengths, such as F87 and P85, could also be used to stabilize the DOPE liposomes. Essentially the same trends were observed when the Pluronics were added to preformed DOPE liposomes instead of being included in the preparation mixture. In this case the least effective copolymers failed, however, to completely prevent the DOPE liposomes from releasing encapsulated hydrophilic markers.

摘要

通过浊度、渗漏和低温透射电子显微镜研究,考察了聚(环氧乙烷)-聚(环氧丙烷)-聚(环氧乙烷)(PEO-PPO-PEO;普朗尼克)共聚物对二油酰磷脂酰乙醇胺(DOPE)脂质体结构和稳定性的影响。结果表明,在DOPE分散体系中加入普朗尼克可以稳定层状Lα相,并制备出在低pH值(pH 5)下稳定且不渗漏的脂质体。观察到稳定能力主要取决于普朗尼克的分子组成。具有相对较长PPO和PEO链段长度的嵌段共聚物,如F127和F108,能最有效地保护在高pH值下制备的DOPE脂质体不发生聚集以及随后由酸化引起的结构重排。发现足够长的PPO嵌段是在低普朗尼克浓度下获得脂质体表面充分覆盖的最关键参数。然而,随着共聚物浓度的增加,具有相对较短PPO和PEO链段长度的普朗尼克,如F87和P85,也可用于稳定DOPE脂质体。当将普朗尼克添加到预先形成的DOPE脂质体中而不是包含在制备混合物中时,观察到基本相同的趋势。不过,在这种情况下,效果最差的共聚物无法完全阻止DOPE脂质体释放包封的亲水性标记物。

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