Herein, we investigated the effects of 2-ethylbutyric acid, 2-ethyl-1-butanol, and 3-methylpentane, each possessing varying functional groups, on polyoxyl 15 hydroxystearate (HS 15) and polysorbate 80 (TW 80) micelles. Initially, the critical micelle concentration (CMC) for both systems was determined. Subsequent measurements included the particle size, zeta potential, cloud point, micropolarity, number of aggregates, and fluorophore release profile. Finally, the number of hydrogen bonds was confirmed through molecular docking technology. Results showed distinct effects of different functional groups on TW 80 and HS 15 micelles, exhibiting a decreasing trend of CMC, Amin, Gmin, particle size, and polydispersity index (PDI) with increased functional group polarity, alongside increased zeta potential, decreased cloud point, enlarged hydrophobic region, and rapid fluorophore quenching. In particular, acids with carboxyl groups exhibited enhanced stability with HS 15 and TW 80 micelles owing to differences in polarity, solubilization sites, and intermolecular forces. Using tanshinone extract as a model drug, the study explored HS 15 and TW 80 micelles as drug carriers, and results indicated that 2-ethylbutyric acid micelles exhibited better bacterial inhibition against Staphylococcus aureus. Considering that the surface of bacteria was negatively charged, the positively charged nanoparticles exhibited strong electrostatic interactions with the bacteria, which exerted a superior antibacterial effect. In summary, 2-ethylbutyric acid micelles displayed the smallest CMC, Amin, Gmin, particle size, and PDI, along with a positive charge, highlighting the potential application of 2-ethylbutyric acid.
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