Sulfated β-Cyclodextrin-Mediated Antimicrobial Peptide Nanoparticles for Alkaloid Encapsulation

The β-cyclodextrin bearing an average of 13 sulfate groups (S₁₃βCD) uniquely combines two key functions: it binds pharmaceutically relevant alkaloids and noncovalently links polycationic antimicrobial peptide chains, enabling the formation of nanoparticles with dual therapeutic potential. In contrast, sulfobutylated β-cyclodextrin does not induce this association, highlighting the significant impact of the butylene spacers on self-assembly.

Dhvar4, a bioactive, cell-penetrating peptide with a net positive charge of +7 at pH 7, was selected for these studies. Its interaction with S₁₃βCD generated nanoparticles with a narrow, uniform size distribution and either positive or negative charges, depending on the molar ratio of the components. The particularly stable, negatively charged nanoparticles efficiently incorporated bioactive plant alkaloids, causing only minor changes in their mean diameter and surface charge. Encapsulation efficiency of the isoquinoline alkaloids correlated with their dimerization ability, with coralyne achieving nearly complete confinement. The high charge density along both the narrow and wide rims of S₁₃βCD enabled the binding of up to 13 coralyne or sanguinarine molecules per macrocycle ― even in the absence of peptide ― likely through a synergistic interplay of electrostatic interactions and π–π stacking between the ligands’ extended aromatic systems.

The chemical formula of coralyne or sanguinarine

The self-assembled S₁₃βCD–Dhvar4–alkaloid system represents the first reported nanoparticles to integrate three bioactive building blocks. This unique combination of functional components may open new opportunities for versatile biomedical applications.

Reference:

Zsombor Miskolczy, Mónika Megyesi, Beáta Mándityné Huszka, István Mándity, László Biczók (2025) Nanoparticle formation of an antimicrobial peptide induced by sulfated β-cyclodextrin: Application to alkaloid encapsulation. Carbohydrate Polymer Technologies and Applications 12, 101053.
https://doi.org/10.1016/j.carpta.2025.101053.