Advanced Alcalase-Coated Clindamycin-Loaded Carbopol Nanogels for Removal of Persistent Bacterial Biofilms

Abstract

Formation of bacterial biofilms in chronic wounds poses a big challenge for effective treatments as their matrix of extracellular polymeric substances provides a protective barrier to surface-attached bacteria against antibiotics. Here, we demonstrate that by surface-functionalizing clindamycin-loaded nanogel particles with the cationic protease, Alcalase 2.4 L FG, a very effective agent for eradicating persistent bacterial biofilms and surpassing antibacterial resistance mechanisms can be developed. The antibiotic nanocarrier used in this study was an Alcalase-coated clindamycin-loaded acrylic copolymer nanogel. Due to the protease surface coating, the functionalized nanogel particles were able to break down the extracellular polymer matrix of biofilms of Gram-positive bacteria, electrostatically attach themselves onto the incorporated bacterial cells, and deliver the antibiotic directly onto their cell walls. We tested the performance of this innovative nanotechnology approach on Staphylococcus aureus. The results showed an increase in biofilm mass reduction of both types of bacterial biofilms compared to treatment with free clindamycin and conventionally used antibacterial agents (cetrimide, benzalkonium chloride, povidone-iodine (PVP-I), and chloroxylenol). The developed dual functionalized antibiotic nanocarrier has proven its effectiveness in treating bacterial biofilms and can potentially find clinical applications for enhanced antibiotic treatments of diabetic foot and chronically infected surface wounds.