关键词: cubosomes drug delivery systems gemini surfactant lipid-based liquid crystalline nanoparticles stability improvement

Mesh : Surface-Active Agents / chemistry Drug Delivery Systems Fatty Alcohols / chemistry Microscopy, Electron, Transmission Particle Size

来  源:   DOI:10.1021/acs.molpharmaceut.3c00378   PDF(Pubmed)

Abstract:
Cubosomes are nanoparticles with bicontinuous cubic internal nanostructures that have been considered for use in drug delivery systems (DDS). However, their low structural stability is a crucial concern for medical applications. Herein, we investigated the use of a gemini surfactant, sodium dilauramidoglutamide lysine (DLGL), which is composed of two monomeric surfactants linked with a spacer to improve the structural stability of cubosomes prepared with phytantriol (PHY). Uniform nanosuspensions comprising a specific mixing ratio of DLGL and PHY in water prepared via ultrasonication were confirmed by using dynamic light scattering. Small-angle X-ray scattering and cryo-transmission electron microscopy revealed the formation of Pn3̅m cubosomes in a range of DLGL/PHY solid ratios between 1 and 3% w/w. By contrast, cubosome formation was not observed at DLGL/PHY solid ratios of 5% w/w or higher, suggesting that excess DLGL interfered with cubosome formation and caused them to transform into small unilamellar vesicles. The addition of phosphate-buffered saline to the nanosuspension caused aggregation when the solid ratio of DLGL/PHY was less than 5% w/w. However, Im3̅m cubosomes were obtained at solid ratios of DLGL/PHY of 6, 7.5, and 10% w/w. The lattice parameters of the Pn3̅m and Im3̅m cubosomes were approximately 7 and 11-13 nm, respectively. The lattice parameters of Im3̅m cubosomes were affected by the concentration of DLGL. Pn3̅m cubosomes were surprisingly stable for 4 weeks at both 25 and 5 °C. In conclusion, DLGL, a gemini surfactant, was found to act as a new stabilizer for PHY cubosomes at specific concentrations. Cubosomes composed of DLGL are stable under low-temperature storage conditions, such as in refrigerators, making them a viable option for heat-sensitive DDS.
摘要:
立方体是具有双连续立方内部纳米结构的纳米颗粒,其已被考虑用于药物递送系统(DDS)。然而,它们的低结构稳定性是医疗应用的关键问题。在这里,我们研究了双子表面活性剂的使用,二月氨基戊胺赖氨酸钠(DLGL),其由与间隔物连接的两种单体表面活性剂组成,以改善用植烷三醇(PHY)制备的立方体的结构稳定性。通过使用动态光散射证实了通过超声处理制备的包含特定混合比的DLGL和PHY在水中的均匀纳米悬浮液。小角度X射线散射和低温透射电子显微镜显示,在1至3%w/w的DLGL/PHY固体比范围内,形成了Pn3m立方体。相比之下,在DLGL/PHY固体比为5%w/w或更高时未观察到立方体形成,表明过量的DLGL干扰了立方体的形成,并导致它们转化为小的单层囊泡。当DLGL/PHY的固体比小于5%w/w时,向纳米悬浮液中添加磷酸盐缓冲盐水引起聚集。然而,以6、7.5和10%w/w的DLGL/PHY的固体比获得3μm立方体。Pn34m和Im34m立方体的晶格参数约为7和11-13nm,分别。DLGL浓度对Im3♪m立方体的晶格参数有一定的影响。在25和5°C下,Pn3äm立方体令人惊讶地稳定了4周。总之,DLGL,双子表面活性剂,被发现在特定浓度下可作为PHY立方体的新稳定剂。由DLGL组成的立方体在低温储存条件下是稳定的,比如在冰箱里,使它们成为热敏DDS的可行选择。
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