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聚(乙二醇)-b-聚(ε-己内酯)和聚乙二醇磷脂在水性介质中形成稳定的混合胶束。

Poly(ethylene glycol)-b-poly(epsilon-caprolactone) and PEG-phospholipid form stable mixed micelles in aqueous media.

作者信息

Vakil Ronak, Kwon Glen S

机构信息

Department of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705, USA.

出版信息

Langmuir. 2006 Nov 7;22(23):9723-9. doi: 10.1021/la061408y.


DOI:10.1021/la061408y
PMID:17073503
Abstract

Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG(5000)-b-PCL(x)) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy poly(ethylene glycol) (PEG-DSPE), possess small size and high thermodynamic stability, raising their potential as long circulating carriers in the context of delivery of antineoplastic and antibiotic drugs. Formation of mixed polymeric micelles was confirmed using size exclusion chromatography and 1H NMR NOESY. Steady-state fluorescence measurements revealed depressed critical micellar concentrations indicative of a cooperative interaction between component hydrophobic blocks, which was quantified using the pseudophase model for micellization. Steady-state fluorescence measurements indicated that the mixed polymeric micelle cores possess intermediate micropolarity and high microviscosity. Pulsed field gradient spin-echo measurements were used to characterize micellar diffusion coefficients, which agree well with those obtained using dynamic light scattering. NOE spectra suggested that the hydrophobic polymer segments from individual components are in close proximity, giving evidence for the formation of a relatively homogeneous core. Contrary to one-component PEG(5000)-b-PCL(x) micelles, the mixed polymeric micelles could incorporate clinically relevant levels of the poorly water soluble antibiotic, amphotericin B (AmB). AmB encapsulation and release studies revealed an interesting composition-dependent interaction of the drug with the mixed polymeric micelle core.

摘要

由生物相容性聚合物聚(乙二醇)-b-聚(ε-己内酯)(PEG(5000)-b-PCL(x))和1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-甲氧基聚(乙二醇)(PEG-DSPE)形成的新型混合聚合物胶束,尺寸小且具有高热力学稳定性,在抗肿瘤和抗生素药物递送方面具有作为长循环载体的潜力。使用尺寸排阻色谱法和1H NMR NOESY证实了混合聚合物胶束的形成。稳态荧光测量显示临界胶束浓度降低,表明组分疏水嵌段之间存在协同相互作用,这使用胶束化的假相模型进行了量化。稳态荧光测量表明混合聚合物胶束核心具有中等微极性和高微粘度。脉冲场梯度自旋回波测量用于表征胶束扩散系数,其与使用动态光散射获得的结果非常吻合。NOE光谱表明来自各个组分的疏水聚合物链段紧密相邻,为形成相对均匀的核心提供了证据。与单组分PEG(5000)-b-PCL(x)胶束相反,混合聚合物胶束可以包封临床相关水平的水溶性差的抗生素两性霉素B(AmB)。AmB的包封和释放研究揭示了药物与混合聚合物胶束核心之间有趣的组成依赖性相互作用。

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