Incorporation of NSAIDs in micelles: implication of structural switchover in drug-membrane interaction

被引:47
作者
Chakraborty, H [1 ]
Banerjee, R [1 ]
Sarkar, M [1 ]
机构
[1] Saha Inst Nucl Phys, Div Chem Sci, Kolkata 700064, W Bengal, India
关键词
COX-inhibitors; oxicam drugs; optical spectroscopy; anisotropy; free energy change; chemical reactivity;
D O I
10.1016/S0301-4622(02)00389-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:315 / 325
页数:11
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