Wiecław Katarzyna, Korchowiec Beata, Corvis Yohann, Korchowiec Jacek, Guermouche Hassan, Rogalska Ewa
Department of Physical Chemistry and Electrochemistry, Faculty of Chemistry, Jagiellonian University, ul. R. Ingardena 3, 30-060 Krakow, Poland.
Langmuir. 2009 Feb 3;25(3):1417-26. doi: 10.1021/la8033897.
Meloxicam, a nonsteroidal anti-inflammatory drug (NSAID), is known as a selective cyclooxygenase-2 inhibitor. Cyclooxygenase-2 is a membrane protein, functionally coupled to an interfacial enzyme, phospholipase A2. Consequently, it may be supposed that the interactions of NSAIDs with lipid membranes play a role in the anti-inflammatory process. In order to investigate the mechanism of this process, Langmuir films formed with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, 1,2-dilauroyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, or 1,2-myristoyl-sn-glycero-3-phosphoethanolamine were exposed to meloxicam and its beta-cyclodextrin inclusion complex. The monolayers were studied by measuring surface pressure, electric surface potential, Brewster angle micrographs, polarization-modulation infrared reflection-absorption spectra, and phospholipase A2 activity; the inclusion complex was studied using molecular modeling. The results obtained show that the monolayers formed in the presence of meloxicam and its complex are expanded and more liquid-like compared to pure lipids. Both compounds modify hydration of the lipid polar heads, orientation of the molecules, morphology of the domains, and the rate of lipolysis catalyzed by phospholipase A2. The latter effect may be involved in the anti-inflammatory activity of meloxicam. Importantly, the effects observed with the meloxicam-beta-cyclodextrin complex are more pronounced compared to those of the free meloxicam. This observation may be relevant for developing new meloxicam preparations with increased bioavailability.
美洛昔康是一种非甾体抗炎药（NSAID），是一种选择性环氧化酶-2抑制剂。环氧化酶-2是一种膜蛋白，在功能上与界面酶磷脂酶A2偶联。因此，可以推测NSAIDs与脂质膜的相互作用在抗炎过程中起作用。为了研究这一过程的机制，将由1,2-二棕榈酰-sn-甘油-3-磷酸胆碱、1,2-二月桂酰-sn-甘油-3-磷酸胆碱、1,2-二棕榈酰-sn-甘油-3-磷酸乙醇胺或1,2-肉豆蔻酰-sn-甘油-3-磷酸乙醇胺形成的朗缪尔膜暴露于美洛昔康及其β-环糊精包合物中。通过测量表面压力、表面电势、布鲁斯特角显微镜图像、偏振调制红外反射吸收光谱和磷脂酶A2活性来研究单层膜；使用分子建模研究包合物。所得结果表明，与纯脂质相比，在美洛昔康及其复合物存在下形成的单层膜更膨胀且更具液体样性质。这两种化合物均会改变脂质极性头部的水合作用、分子取向、结构域形态以及磷脂酶A2催化的脂解速率。后一种效应可能与美洛昔康的抗炎活性有关。重要的是，与游离美洛昔康相比，美洛昔康-β-环糊精复合物观察到的效应更明显。这一观察结果可能与开发具有更高生物利用度的新美洛昔康制剂相关。
