Sokol Maria B, Sokhraneva Vera A, Groza Nataliya V, Mollaeva Mariia R, Yabbarov Nikita G, Chirkina Margarita V, Trufanova Anna A, Popenko Vladimir I, Nikolskaya Elena D
N.M. Emanuel Institute of Biochemical Physics of Russian Academy of Sciences, 119334 Moscow, Russia.
N.A. Preobrazhensky Department of Chemistry and Technology of Biologically Active Compounds, Medicinal and Organic Chemistry, M.V. Lomonosov Institute of Fine Chemical Technologies, MIREA-Russian Technological University, 119571 Moscow, Russia.
Polymers (Basel). 2023 Dec 26;16(1):72. doi: 10.3390/polym16010072.
Unsaturated fatty acids, such as oleic acid (OA) and linoleic acid (LA), are promising antimicrobial and cytostatic agents. We modified OA and LA with thymol (TOA and TLA, respectively) to expand their bioavailability, stability, and possible applications, and encapsulated these derivatives in polymeric nanoparticles (TOA-NPs and TLA-NPs, respectively). Prior to synthesis, we performed mathematical simulations with PASS and ADMETlab 2.0 to predict the biological activity and pharmacokinetics of TOA and TLA. TOA and TLA were synthesized via esterification in the presence of catalysts. Next, we formulated nanoparticles using the single-emulsion solvent evaporation technique. We applied dynamic light scattering, Uv-vis spectroscopy, release studies under gastrointestinal (pH 1.2-6.8) and blood environment simulation conditions (pH 7.4), and in vitro biological activity testing to characterize the nanoparticles. PASS revealed that TOA and TLA have antimicrobial and anticancer therapeutic potential. ADMETlab 2.0 provided a rationale for TOA and TLA encapsulation. The nanoparticles had an average size of 212-227 nm, with a high encapsulation efficiency (71-93%), and released TOA and TLA in a gradual and prolonged mode. TLA-NPs possessed higher antibacterial activity against and and pronounced cytotoxic activity against MCF-7, K562, and A549 cell lines compared to TOA-NPs. Our findings expand the biomedical application of fatty acids and provide a basis for further in vivo evaluation of designed derivatives and formulations.
不饱和脂肪酸，如油酸（OA）和亚油酸（LA），是很有前景的抗菌和细胞生长抑制剂。我们用百里酚分别对OA和LA进行修饰（分别得到TOA和TLA），以扩大它们的生物利用度、稳定性及可能的应用范围，并将这些衍生物分别封装在聚合物纳米颗粒（TOA-NPs和TLA-NPs）中。在合成之前，我们使用PASS和ADMETlab 2.0进行数学模拟，以预测TOA和TLA的生物活性和药代动力学。TOA和TLA是在催化剂存在下通过酯化反应合成的。接下来，我们采用单乳液溶剂蒸发技术制备纳米颗粒。我们应用动态光散射、紫外可见光谱、在胃肠道（pH 1.2 - 6.8）和血液环境模拟条件（pH 7.4）下的释放研究以及体外生物活性测试来表征这些纳米颗粒。PASS显示TOA和TLA具有抗菌和抗癌治疗潜力。ADMETlab 2.0为TOA和TLA的封装提供了理论依据。这些纳米颗粒的平均尺寸为212 - 227 nm，具有较高的封装效率（71 - 93%），并以逐渐且持久的方式释放TOA和TLA。与TOA-NPs相比，TLA-NPs对[具体细菌名称1]和[具体细菌名称2]具有更高的抗菌活性，对MCF-7、K562和A549细胞系具有显著的细胞毒性活性。我们的研究结果扩展了脂肪酸的生物医学应用，并为进一步体内评估设计的衍生物和制剂提供了基础。
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