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001028278 1001_ $$0P:(DE-HGF)0$$aRai, Ragini$$b0
001028278 245__ $$aAlkanols Regulate the Fluidity of Phospholipid Bilayer in Accordance to Their Concentration and Polarity
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001028278 520__ $$aIn spite of the widespread use of alkanols as penetration enhancers, their effect on vesicular formulations remains largely unexplored. These can affect the stability and integrity of the phospholipid bilayers. In this study, we have investigated the interaction of linear (ethanol, butanol, hexanol, octanol) and branched alkanols (t-amylol and t-butanol) with three phospholipids (soya lecithin, SL; soy L-α-phosphatidylcholine, SPC; and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC). Thermodynamic and structural aspects of these interactions were studied as a function of the alkanol concentration and chain length. Our interpretations are based on isothermal titration calorimetry (ITC) and dynamic light scattering (DLS) experiments. We observed one-site interactions wherein hydroxyl and acyl groups interacted with the polar and nonpolar regions of the phospholipid, respectively. The stability and structural integrity of bilayers appeared to be dependent upon (a) the hydrocarbon chain length and concentration of alcohols, and (b) the degree of unsaturation in the phospholipid molecule. We found that these interactions triggered a reduction in the enthalpy which was compensated by increased entropy, keeping free energy negative. Drop in enthalpy indicates reversible disordering of the bilayer which enables the diffusion of alcohol without triggering destabilization. Ethanol engaged predominantly with the interface, and it resulted in higher enthalpic changes. Interactions became increasingly unfavorable with longer alcohols – a cutoff point was recorded with hexanol. The overall sequence of membrane disordering capability was recorded as follows: ethanol < butanol < octanol < hexanol. Octanol’s larger size restricted its penetration in the bilayer, and hence it caused less enthalpic changes relative to hexanol. This could also be verified from the trends in the area ratio of these vesicles obtained from the DLS data. Branched alkanols displayed a lower binding affinity with the phospholipids relative to their linear counterparts. These data are useful while contemplating the inclusion of short-chain alcohols as penetration enhancers in phospholipid vesicles.
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001028278 7001_ $$0P:(DE-HGF)0$$aKumar, Deepak$$b1
001028278 7001_ $$0P:(DE-HGF)0$$aDhule, Anjali A.$$b2
001028278 7001_ $$0P:(DE-Juel1)201210$$aRudani, Binny$$b3$$ufzj
001028278 7001_ $$00000-0001-7898-7974$$aTiwari, Sanjay$$b4$$eCorresponding author
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