Combined Effects of Ethanol Co-solvent and Cholesterol Additive on the Structural Mechanical and Phase Properties of Ion Pair Amphiphile Bilayers: A Molecular Dynamics Study

  • 賴 宇芳

Student thesis: Doctoral Thesis

Abstract

Ion pair amphiphile (IPA) is a molecular complex composed of a pair of cationic and anionic amphiphiles IPA can self-assemble into catanionic vesicles as potential drug carriers that are considered as low-cost liposome alternatives Experimental results showed that the poor stability of catanionic vesicles can be improved by the way of ethanol co-solvent and cholesterol additive Yet the combination of ethanol and cholesterol can also induce complex phase behavior of IPA membranes In this work we utilized molecular dynamics (MD) simulation to examine the effect of ethanol co-solvent and cholesterol additive on the structural mechanical and phase properties of symmetrical alkyltrimethylammonium-alkylsulfate (CnTMA+-CnS-) IPA bilayer systems Our result showed that increasing ethanol concentration can disrupt the packing order of the bilayers hydrophobic region and induces liquid-disordered phase formation Also the packing order of short-chained systems are easily disrupted by penetrated ethanol Furthermore the ethanol co-solvent can reduce mechanical strength of IPA membrane In contrast the cholesterol addition can enhance mechanical strength of the membrane but have complex alkyl chain ordering effects on IPA membranes in different chain lengths The C12TMA-C12S IPA systems has shorter chains than cholesterol molecule leading to an enhanced ordering effect even in gel phase membranes In contrast the C16TMA-C16S IPA systems is longer than cholesterol; and adding cholesterol can disrupt the alkyl chain packing order within the membrane Combining both ethanol co-solvent and cholesterol additive high XChol inhibits ethanol insertion within membrane At XChol=0 5 cholesterol insertion induces the separation between IPA complexes particularly within the hydrophilic region Thus ethanol can penetrate the head group region of the IPA membrane; yet ethanol still cannot permeate into the densely packed hydrophobic region Furthermore the number of permeate ethanol within the membrane hydrophobic region is highly correlated to the changes in the alkyl chain order parameters Ethanol can also reduce the local bilayer thickness leading to double membrane thickness distributions These results helped confirm the coexistence of dual phases induced by cholesterol and ethanol Based on the simulation results of structural and mechanical properties we determined the characteristic values of different phases and proposed the phase diagrams for C12TMA-C12S C14TMA-C14S and C16TMA-C16S systems under the effects of ethanol co-solvent and cholesterol additive The molecular insights provided by our results can shed lights on future designs of novel ethosome-like IPA vesicles with most optimized formula as drug carriers for transdermal drug delivery applications
Date of Award2020
Original languageEnglish
SupervisorChi-cheng Chiu (Supervisor)

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