Lopes Sávia C A, Novais Marcus V M, Ferreira Diêgo S, Braga Fernão C, Magalhães-Paniago Rogério, Malachias Ângelo, Oliveira Mônica C
Faculty of Pharmacy, and ‡Physics Department, Institute of Exact Sciences, Universidade Federal de Minas Gerais , Belo Horizonte, Minas Gerais 31270-901, Brazil.
Langmuir. 2014 Dec 23;30(50):15083-90. doi: 10.1021/la502977j. Epub 2014 Dec 9.
Ursolic acid (UA) is a triterpene found in different plant species that has been shown to possess significant antitumor activity. However, UA presents a low water solubility, which limits its biological applications. In this context, our research group has proposed the incorporation of UA in long-circulating and pH-sensitive liposomes (SpHL-UA).These liposomes, composed of dioleylphosphatidylethanolamine (DOPE), cholesteryl hemisuccinate (CHEMS), and distearoylphosphatidylethanolamine-polyethylene glycol2000 (DSPE-PEG2000), were shown to be very promising carriers for UA. Considering that the release of UA from SpHL-UA and its antitumor activity depend upon the occurrence of the lamellar to non-lamellar phase transition of DOPE, in the present work, the interactions of UA with the components of the liposomes were evaluated, aiming to clarify their role in the structural organization of DOPE. The study was carried out by differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) under low hydration conditions. DSC studies revealed that DOPE phase transition temperatures did not shift significantly upon UA addition. On the other hand, in SAXS studies, a different pattern of DOPE phase organization was observed in the presence of UA, with the occurrence of the cubic phase Im3m at 20 °C and the cubic phase Pn3m at 60 °C. These findings suggest that UA interacts with the lipids and changes their self-assembly. However, these interactions between the lipids and UA were unable to eliminate the lamellar to non-lamellar phase transition, which is essential for the cytoplasmic delivery of UA molecules from SpHL-UA.
熊果酸（UA）是一种存在于不同植物物种中的三萜类化合物，已被证明具有显著的抗肿瘤活性。然而，UA的水溶性较低，这限制了其生物学应用。在此背景下，我们的研究小组提出将UA包封于长循环且pH敏感的脂质体（SpHL-UA）中。这些脂质体由二油酰磷脂酰乙醇胺（DOPE）、胆固醇半琥珀酸酯（CHEMS）和二硬脂酰磷脂酰乙醇胺-聚乙二醇2000（DSPE-PEG2000）组成，被证明是UA非常有前景的载体。考虑到UA从SpHL-UA中的释放及其抗肿瘤活性取决于DOPE从片层相向非片层相的转变，在本研究中，评估了UA与脂质体各组分的相互作用，旨在阐明它们在DOPE结构组织中的作用。该研究在低水合条件下通过差示扫描量热法（DSC）和小角X射线散射（SAXS）进行。DSC研究表明，添加UA后DOPE的相变温度没有显著变化。另一方面，在SAXS研究中，在存在UA的情况下观察到DOPE相组织的不同模式，在20℃时出现立方相Im3m，在60℃时出现立方相Pn3m。这些发现表明UA与脂质相互作用并改变其自组装。然而，脂质与UA之间的这些相互作用并不能消除片层相向非片层相的转变，而这对于UA分子从SpHL-UA向细胞质的递送至关重要。
