Self-Aggregation, Antibacterial Activity, and Mildness of Cyclodextrin/Cationic Trimeric Surfactant Complexes.

Abstract

Despite efficacious antimicrobial activity, cationic oligomeric surfactants show strong skin irritation potential due to their larger cationic charge numbers and multiple hydrophobic chains. This work reports that the incorporation of α-, β-, and γ-CDs with different cavity sizes can effectively improve the mildness of cationic ammonium trimeric surfactant DTAD with a star-shaped spacer while maintaining its high antibacterial activity. On the basis of the different cavity sizes of CDs and the asymmetry in the spacer of DTAD, the CD/DTAD mixtures form α-CD@DTAD, 2α-CD@DTAD, β-CD@DTAD, and γ-CD@DTAD complexes. Compared to DTAD, these CD/DTAD complexes show much stronger self-assembly ability with much lower critical aggregation concentrations (CAC) and form more diverse aggregates with reduced zeta potential. Just above their CACs, the CD/DTAD complexes form vesicles or solid spherical aggregates of ∼50 nm and then transform into small micelles of ∼10 nm as the concentration increases. The strong self-assembly ability and the multiple sites of hydrogen bonds of the CD/DTAD complexes endow them with high antibacterial activity against E. coli, showing a very low minimum inhibitory concentration (2.22-2.48 μM) comparable to that of DTAD. In particular, the addition of CDs significantly reduces the abilities of DTAD in solubilizing zein (a skin model protein) and in binding with zein, and the mildness decreases in the order of 2α-CD@DTAD > β-CD@DTAD > γ-CD@DTAD > α-CD@DTAD. This tendency depends on their different self-assembling structures, and the formation of vesicles is approved to be in favor of the improvement of the mildness.