Incorporation of NSAIDs in micelles: implication of structural switchover in drug-membrane interaction
Incorporation of NSAIDs in micelles: implication of structural switchover in drug-membrane interaction
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DOI：
10.1016/s0301-4622(02)00389-7
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发表时间：
2003-05-01
影响因子：
3.8
通讯作者：
Sarkar, M
中科院分区：
文献类型：
--
作者：
Chakraborty, H;Banerjee, R;Sarkar, M
昔康类非甾体抗炎药（NSAIDs）不仅具有抗炎作用，而且具有多种功能。它们的主要靶标是环加氧酶，这是一种膜相关酶。为了与靶点结合，这些药物必须穿过膜，因此它们与生物膜的相互作用应该在指导它们与环加氧酶的相互作用中发挥主要作用。在这里，我们研究了三个非甾体抗炎药的昔康组，即吡罗昔康，美洛昔康和替诺昔康胶束具有不同的头基电荷，作为简单的膜模拟系统的相互作用。光谱方法已被用来了解这些药物与十六烷基N，N，N-三甲基溴化铵（阳离子），十二烷基磺酸钠（阴离子）和Triton X-100（中性）胶束的相互作用。我们的研究结果表明，药物的环境，即胶束的性质在选择特定的亲质子形式的药物掺入中起着决定性的作用。此外，它诱导吡罗昔康不同亲质子形式之间的转换或变化，这与存在不同表面电荷时其反应性的变化相关，由pK（a）值的变化给出。这些结果共同表明，在体内，生物膜的多样性可能在选择将呈现给其靶标的特定形式的昔康NSAID中发挥重要作用。(C)2003 Elsevier Science B. V.保留所有权利。
Non-steroidal anti-inflammatory drugs (NSAIDs) of oxicam group are not only effective as anti-inflammatory agents but also show diverse functions. Their principal targets are cyclooxygenases, which are membrane-associated enzymes. To bind with the targets these drugs have to pass through the membrane and hence their interactions with biomembranes should play a major role in guiding their interactions with cyclooxygenases. Here we have studied the interactions of three NSAIDs of oxicam group viz. piroxicam, meloxicam and tenoxicam with micelles having different headgroup charges, as simple membrane mimetic systems. Spectroscopic methods have been used to understand the interaction of these drugs with Cetyl N,N,N-trimethyl ammonium bromide (cationic), Sodium dodecyl sulphonate (anionic) and Triton X-100 (neutral) micelles. Our results demonstrate that the environment of the drugs i.e. the nature of the micelles plays a decisive role in choosing a specific prototropic form of the drugs for incorporation. Additionally it induces a switch over or change between different prototropic forms of piroxicam, which is correlated with the change in their reactivities in presence of different surface charges, given by the change in pK(a) values. These results together, indicate that in vivo, the diverse nature of biomembranes might play a significant role in choosing the particular form of oxicam NSAIDs that would be presented to their targets. (C) 2003 Elsevier Science B.V. All rights reserved.