The modulation of surfactant and drug self-assembly by ionic liquids (ILs) is a key strategy for enhancing the efficacy of drug delivery and antimicrobial systems. This study investigates the micellization behaviour of cetylpyridinium chloride (CPC), a cationic surfactant, in the absence and presence of ionic liquids (ILs), namely 1-butyl-1-methylpiperidinium chloride ([C4C1pip][Cl]) and 1-butyl-1-methylpiperidinium bromide ([C4C1pip][Br]). Furthermore, the interaction of CPC with the antidepressant drug amitriptyline hydrochloride (AMT) was analysed in IL media to evaluate the mixed micellization behaviour. Conductometric measurements at various temperatures revealed that both piperidinium ILs significantly lower the CMC of CPC, with the bromide IL inducing a more pronounced effect. Thermodynamic parameters (<InlineEquation ID="IEq1"> <EquationSource Format="TEX">\({{\Delta}\:\text{G}}_{m}^{o}\)</EquationSource> </InlineEquation>, <InlineEquation ID="IEq2"> <EquationSource Format="TEX">\({{\Delta}\:\text{H}}_{m}^{o}\)</EquationSource> </InlineEquation>, and <InlineEquation ID="IEq3"> <EquationSource Format="TEX">\({{\Delta}\:\text{S}}_{m}^{o}\)</EquationSource> </InlineEquation>) were calculated to understand the spontaneity, enthalpic/entropic contributions, and the role of ILs in modulating aggregation. The findings show that adding ILs significantly lowers the CMC of CPC, suggesting improved micellar stability resulting from the combined effects of hydrophobic and electrostatic interactions. Strong synergism in the CPC–AMT mixed systems is confirmed by the negative values of the interaction parameter (<InlineEquation ID="IEq4"> <EquationSource Format="TEX">\({\beta}\;^{m}\)</EquationSource> </InlineEquation>). Moreover, the molecular-level experimental data are supported by quantum-chemical simulations that provide insight into the relative stability and reactivity of CPC, AMT, as well as the ILs [C4C1pip][Cl] and [C4C1pip][Br]. The antibacterial activity of CPC, AMT, ILs, and their binary and ternary mixtures was estimated against Escherichia coli (E. Coli) and Staphylococcus aureus (S. aureus). The enhanced activity is attributed to the cooperative membrane-disrupting capability of the surfactant, IL, and drug molecules. Overall, the study demonstrates that ILs can effectively modulate micellar self-assembly and enhance biological performance, offering promising prospects for the design of multifunctional drug delivery and antimicrobial systems.

Exploring the effect of piperidinium-based ionic liquids on the cetylpyridinium chloride and amitriptyline hydrochloride system: micellization, density function theory and antibacterial activity

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发表日期：

2026年5月12日

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Nafseen Ahmed,
Mohammad Tariq,
Juhi Saraswat,
Rajan Patel,
Mohd Sajid Ali,
Abbul Bashar Khan

摘要

The modulation of surfactant and drug self-assembly by ionic liquids (ILs) is a key strategy for enhancing the efficacy of drug delivery and antimicrobial systems. This study investigates the micellization behaviour of cetylpyridinium chloride (CPC), a cationic surfactant, in the absence and presence of ionic liquids (ILs), namely 1-butyl-1-methylpiperidinium chloride ([C₄C₁pip][Cl]) and 1-butyl-1-methylpiperidinium bromide ([C₄C₁pip][Br]). Furthermore, the interaction of CPC with the antidepressant drug amitriptyline hydrochloride (AMT) was analysed in IL media to evaluate the mixed micellization behaviour. Conductometric measurements at various temperatures revealed that both piperidinium ILs significantly lower the CMC of CPC, with the bromide IL inducing a more pronounced effect. Thermodynamic parameters ( \({{\Delta}\:\text{G}}_{m}^{o}\) , \({{\Delta}\:\text{H}}_{m}^{o}\) , and \({{\Delta}\:\text{S}}_{m}^{o}\) ) were calculated to understand the spontaneity, enthalpic/entropic contributions, and the role of ILs in modulating aggregation. The findings show that adding ILs significantly lowers the CMC of CPC, suggesting improved micellar stability resulting from the combined effects of hydrophobic and electrostatic interactions. Strong synergism in the CPC–AMT mixed systems is confirmed by the negative values of the interaction parameter ( \({\beta}\;^{m}\) ). Moreover, the molecular-level experimental data are supported by quantum-chemical simulations that provide insight into the relative stability and reactivity of CPC, AMT, as well as the ILs [C₄C₁pip][Cl] and [C₄C₁pip][Br]. The antibacterial activity of CPC, AMT, ILs, and their binary and ternary mixtures was estimated against Escherichia coli (E. Coli) and Staphylococcus aureus (S. aureus). The enhanced activity is attributed to the cooperative membrane-disrupting capability of the surfactant, IL, and drug molecules. Overall, the study demonstrates that ILs can effectively modulate micellar self-assembly and enhance biological performance, offering promising prospects for the design of multifunctional drug delivery and antimicrobial systems.