Mazzoni Serena, Barbosa Leandro R S, Funari Sergio S, Itri Rosangela, Mariani Paolo
Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche , Ancona 60121, Italy.
Instituto de Fisica, Universidade de São Paulo , São Paulo 05508-020, Brazil.
Langmuir. 2016 Jan 26;32(3):873-81. doi: 10.1021/acs.langmuir.5b03507. Epub 2016 Jan 13.
Structural properties and polymorphism of monoolein (MO) in aqueous solutions have been studied for a long time, and the final picture can be considered definite. The presence of bicontinuous phases and the ability to encapsulate hydrophilic, hydrophobic, and amphiphilic compounds, together with the capability to protect and slowly release the entrapped molecules, designated MO phases as good matrices for the sustained release of drugs. Because phase stability, loading efficiency, and bioavailability are strongly correlated, the interplay between MO phases and entrapped compounds is worthy of investigation. In this paper, low angle X-ray diffraction has been used to describe the effects of a model protein (the cytochrome-c) on the monoolein cubic phases as a function of both incubation time and protein concentration in the soaking solutions. Results show that the MO polymorphism is strongly modified by the protein, underlying the very large affinity of the cytochrome-c toward monoolein. However, the different phases have a different sensibility to cytochrome-c, as phase transitions occur when the protein amount exceeds some different critical values, probably related to the structure characteristics (2 cytochrome-c per unit cell at the Pn3m to Im3m cubic phase transition and 10-20 cytochrome-c per unit cell at the Im3m to P4332 cubic phase transition). Moreover, although equilibration times resulted to be quite long (more than 10 days), the fraction of cytochrome-c incorporated into the MO phases is very high (up to 20% v/v inside the P4332 cubic phase). Such results are intriguing: even if they may be specific to the cytochrome-c/MO case, the need of assessing the structural characteristics of lipid matrices before their use as drug delivery systems is evident.
单油酸甘油酯（MO）在水溶液中的结构性质和多晶型现象已被研究了很长时间，最终的情况可以认为是确定的。双连续相的存在以及包封亲水性、疏水性和两亲性化合物的能力，再加上保护和缓慢释放被包封分子的能力，使MO相成为药物缓释的良好基质。由于相稳定性、负载效率和生物利用度密切相关，MO相和被包封化合物之间的相互作用值得研究。在本文中，低角度X射线衍射已被用于描述模型蛋白（细胞色素c）对单油酸甘油酯立方相的影响，该影响是浸泡溶液中孵育时间和蛋白质浓度的函数。结果表明，蛋白质对MO多晶型有强烈影响，这表明细胞色素c对单油酸甘油酯具有非常大的亲和力。然而，不同相对细胞色素c的敏感性不同，因为当蛋白质量超过一些不同的临界值时会发生相变，这些临界值可能与结构特征有关（在Pn3m到Im3m立方相转变时每个晶胞有2个细胞色素c，在Im3m到P4332立方相转变时每个晶胞有10 - 20个细胞色素c）。此外，尽管平衡时间很长（超过10天），但掺入MO相的细胞色素c的比例非常高（在P4332立方相内高达20% v/v）。这些结果很有趣：即使它们可能特定于细胞色素c/MO的情况，但在将脂质基质用作药物递送系统之前评估其结构特征的必要性是显而易见的。
