title: Interaction of oxicam NSAIDs with DMPC vesicles: differential partitioning of drugs.
abstract: Small unilamellar vesicles (SUVs) formed by the dimyristoylphosphatidylcholine (DMPC), a phospholipid; serve as a membrane mimetic system that can be used to study the effect of absence of net surface charges on drug-membrane interaction. The targets of non-steroidal anti-inflammatory drugs (NSAIDs) are cyclooxygenases, which are membrane active enzymes. Hence, to approach their targets NSAIDs have to pass different bio-membranes. Different membrane parameters are expected to guide the first level of interaction of these drugs before they are presented to their targets. Our earlier studies have demonstrated the crucial role of surface charges of membrane mimetic systems like micelles and mixed micelles on the interaction of oxicam NSAIDs. In order to see whether net surface charges of membranes are essential for the interaction of oxicam NSAIDs, we have studied the incorporation of two oxicam NSAIDs, viz., piroxicam and meloxicam in DMPC vesicles using the intrinsic fluorescence properties of the drugs. To see whether different prototropic forms of the drugs can interact with DMPC vesicles, studies were carried out under different pH conditions. Transmission electron microscopy (TEM) was used to characterize the SUVs those were formed at different pH values. Steady state fluorescence anisotropy measurements show that both forms of the two drugs, viz., global neutral and anion can be incorporated into the DMPC vesicles. Partition coefficient (KP) between DMPC and the aqueous buffer used has been calculated in all cases from fluorescent intensity measurements. The KP values for the neutral and anionic forms of piroxicam are 219.0 and 25.8, respectively, and that for meloxicam are 896.7 and 110.2, respectively. From the KP values it is evident that irrespective of the nature of the prototropic forms, meloxicam has a higher KP value than piroxicam. This correlates with the previously calculated log KP values between n-octanol and aqueous phase, which demonstrates that in absence of net surface charges of DMPC vesicles the hydrophobic interaction is the principal driving force for incorporation. Our results imply that for bio-membranes having no net surface charges hydrophobic effect plays a principal role to guide these NSAIDs to their targets.
authors.affiliation: Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Calcutta 700064, India.
authors.forename: Hirak
authors.initials: H
authors.lastname: Chakraborty
authors.forename: Sujata
authors.initials: S
authors.lastname: Roy
authors.forename: Munna
authors.initials: M
authors.lastname: Sarkar
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D000077239:Meloxicam; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D044367:Phase Transition; D010894:Piroxicam / Q000737:chemistry*; D013843:Thiazines / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008823:Micelles; D013843:Thiazines; D013844:Thiazoles; D010894:Piroxicam; D015060:1,2-Dipalmitoylphosphatidylcholine; D000077239:Meloxicam