Enhanced antimicrobial treatment by a clay-based drug nanocarrier conjugated to a guanidine-rich cell penetrating peptide

Abstract

In this study, a novel and efficient drug delivery system is proposed for the enhancement of antimicrobial properties of antibiotic medications such as vancomycin (VCM) and levofloxacin (OFX). The architecture of the designed drug carrier is based on halloysite nanotubes (HNTs) with a rolled-laminate shape, suitable for the encapsulation of drug and further release. In order to make them capable for magnetic direction to the target tissue, the exterior surface of the tubes is composed of iron oxide nanoparticles (Fe₃O₄ NPs), via an in situ process. The main role in the antimicrobial activity enhancement is played by a cell-penetrating peptide (CPP) sequence synthesized in the solid phase, which contains three arginine–tryptophan blocks plus a cysteine as the terminal amino acid (C(WR)₃). The drug content values for the prepared nanocargoes named as VCM@Fe₃O₄/HNT–C(WR)₃ and OFX@Fe₃O₄/HNT–C(WR)₃, have been estimated at ca. 10 wt% and 12 wt%, respectively. Also, the drug release investigations have shown that above 90% of the encapsulated drug is released in acetate buffer (pH = 4.6), during a 90 minutes process. Confocal microscopy has corroborated good adhesion and co-localization of the particles and the stained living cells. Moreover, in vitro antimicrobial assessments (optical density, zone of inhibition, and minimum inhibitory concentration) have revealed that the bacterial cell growth rate is significantly inhibited by suggested nanocargoes, in comparison with the individual drugs in the same dosage. Hence, administration of the presented nanocargoes is recommended for the clinical treatment of the infected target organ.