Detection of Drug-Membrane Interactions in Individual Phospholipid Vesicles by Confocal Raman Microscopy

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• 作者：Christopher B. Fox ; Robert A. Horton ; and Joel M. Harris
• 刊名：Analytical Chemistry
• 出版年：2006
• 出版时间：July 15, 2006
• 年：2006
• 卷：78
• 期：14
• 页码：4918 - 4924
• 全文大小：178K
• 年卷期：v.78,no.14(July 15, 2006)
• ISSN：1520-6882

文摘

Optical-trapping confocal Raman microscopy is developedas a method to study the interactions of drugs or othercompounds with the membranes of individual phospholipid vesicles. This technique allows membrane disorder,permeability, and drug localization to be assessed withoutthe need for labeling of the membrane or the compoundsof interest. We have applied this technique to study theinteractions of two nonsteroidal antiinflammatory drugs,salicylate and ibuprofen, with vesicles prepared from 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Theresults show that both salicylate and ibuprofen increasemembrane disorder, as determined from increases in theRaman scattering from gauche conformers in the phospholipid acyl chains. By monitoring the Raman scatteringof the drug molecules in optically trapped DMPC vesicles,the membrane permeability and partitioning of the drugscould be determined; the spatial distributions of the drugswere also measured by scanning the laser focus throughsurface-adhered 1,2-dipalmitoyl-sn-glycero-3-phosphocholine vesicles, producing a profile of the vesicle and itscontents. Though the membrane is permeable to bothdrugs, ibuprofen preferentially accumulates in the membrane, whereas salicylate does not. The measured ibuprofen accumulation agrees quantitatively with the water/octanol partition coefficient of the drug and the estimatedvolume of the lipid membrane. The results suggest thatibuprofen localizes in the hydrophobic acyl chain regionof the membrane, whereas salicylate weakly associateswith the phospholipid headgroups.