Kristensen Søren, Hassan Khadeija, Andersen Nadia Skarnager, Steiniger Frank, Kuntsche Judith
Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark.
Center for Electron Microscopy, Jena University Hospital, Jena, Germany.
Front Med Technol. 2023 Sep 6;5:1241368. doi: 10.3389/fmedt.2023.1241368. eCollection 2023.
Cochleates are cylindrical particles composed of dehydrated phospholipid bilayers. They are typically prepared by addition of calcium ions to vesicles composed of negatively charged phospholipids such as phosphatidylserines (PS). Due to their high physical and chemical stability, they provide an interesting alternative over other lipid-based drug formulations for example to improve oral bioavailability or to obtain a parenteral sustained-release formulation.
In the present study, the feasibility to prepare cochleate suspensions from soy lecithin-derived phosphatidylserines (SPS) was investigated and compared to the "gold standard" dioleoyl-phosphatidylserine (DOPS) cochleates. The SPS lipids covered a large range of purities between 53 and >96% and computer-controlled mixing was evaluated for the preparation of the cochleate suspensions. Electron microscopic investigations were combined with small-angle x-ray diffraction (SAXD) and Laurdan generalized polarization (GP) analysis to characterize particle structure and lipid organization.
Despite some differences in particle morphology, cochleate suspensions with similar internal lipid structure as DOPS cochleates could be prepared from SPS with high headgroup purity (≥96%). Suspensions prepared from SPS with lower purity still revealed a remarkably high degree of lipid dehydration and well-organized lamellar structure. However, the particle shape was less defined, and the typical cochleate cylinders could only be detected in suspensions prepared with higher amount of calcium ions. Finally, the study proves the feasibility to prepare suspensions of cochleates or cochleate-like particles directly from a calcium salt of soy-PS by dialysis.
耳蜗状结构是由脱水磷脂双层组成的圆柱形颗粒。它们通常是通过向由带负电荷的磷脂（如磷脂酰丝氨酸（PS））组成的囊泡中添加钙离子来制备的。由于其高物理和化学稳定性，与其他基于脂质的药物制剂相比，它们提供了一种有趣的替代方案，例如用于提高口服生物利用度或获得肠胃外缓释制剂。
在本研究中，研究了从大豆卵磷脂衍生的磷脂酰丝氨酸（SPS）制备耳蜗状结构悬浮液的可行性，并与“金标准”二油酰磷脂酰丝氨酸（DOPS）耳蜗状结构进行了比较。SPS脂质的纯度范围在53%至>96%之间，对制备耳蜗状结构悬浮液的计算机控制混合进行了评估。电子显微镜研究与小角X射线衍射（SAXD）和劳丹广义极化（GP）分析相结合，以表征颗粒结构和脂质组织。
尽管颗粒形态存在一些差异，但可以从具有高头部基团纯度（≥96%）的SPS制备出与DOPS耳蜗状结构具有相似内部脂质结构的耳蜗状结构悬浮液。由较低纯度的SPS制备的悬浮液仍然显示出非常高的脂质脱水程度和组织良好的层状结构。然而，颗粒形状不太明确，只有在使用较高量钙离子制备的悬浮液中才能检测到典型的耳蜗状圆柱体。最后，该研究证明了通过透析直接从大豆PS钙盐制备耳蜗状结构或类耳蜗状颗粒悬浮液的可行性。
