Peptides: β‐Cyclodextrin Inclusion Compounds as Highly Effective Antimicrobial and Anti‐Epithelial Proliferation Agents

Background: The use of antimicrobial peptides (AMPs) as therapeutic agents for periodontal infections has great advantages, such as broad spectrum of action, low toxicity, and limited bacterial resistance. However, their practical use is limited because of the large amount of peptide required to exercise the microbicidal function. Methods: LyeTxI, LL37f, and KR12 cationic peptides were prepared with β‐cyclodextrin (βCD) at 1:1 molar ratios. The susceptibility of Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Fusobacterium nucleatum were assessed in anaerobic conditions. Cytotoxicity assays were performed using osteoblast and Caco‐2 epithelial cells, and hemolytic activity was assessed on rabbit erythrocytes at an absorbance of 414 nm. Parameters of surface roughness and electrical charge were established by atomic force microscopy and zeta (ζ) potential, respectively. Results: AMP/βCDs drastically decreased the peptide concentration required for activity against the bacteria tested. Moreover, AMPs associated with βCD were able to modify cell‐surface parameters, such as roughness and ζ potential. On the other hand, AMP/βCD did not alter the degree of hemolysis induced by the pure AMPs. The effective concentration at half‐maximum values of the peptides and compounds on osteoblasts were greater than the concentrations required to achieve inhibition of bacterial growth in all the species tested. AMP/βCDs inhibited the proliferation of Caco‐2 epithelial cells in a more efficient manner than AMPs alone. Conclusion: AMP/βCD compounds more effectively inhibit periodontopathogenic bacteria than AMPs alone, with the additional ability of inhibiting the proliferation of epithelial cells at concentrations that are non‐cytotoxic for osteoblasts and erythrocytes.