Boosting the antimicrobial action of vancomycin formulated in shellac nanoparticles of dual-surface functionality

Abstract

We report a strong amplification of the antimicrobial action of vancomycin (VCM) encapsulated in shellac nanoparticles (NPs) with dual surface functionalisation. These shellac nanocarriers for VCM were produced in two steps: (i) a pH drop from aqueous ammonium shellac solution containing Poloxamer 407 (P407) as a steric stabilising polymer in solution of vancomycin hydrochloride, and (ii) subsequent doping with the insoluble cationic surfactant octadecyltrimethylammonium bromide (ODTAB) though a solvent change to yield cationic surface functionality. We evaluated the encapsulation efficiency of VCM and its release profiles from these nanocarriers. This study explored the antibiotic action of these VCM nanocarriers at the various stages of their preparation which helped us to evaluate how they could be made to work efficiently, to adapt their design and demonstrate the role of the nanocarrier dual functionalisation on its antibiotic action and delivery. The antibiotic effect of VCM loaded in such versatile functionalised shellac nanocarriers was tested on three different proxy microorganisms, C. reinhardtii, S. cerevisiae and E. coli. We also compared the antibiotic effect of free VCM with non-coated VCM-loaded nanocarriers at the same overall concentrations. The ODTAB coating of the shellac NPs strongly enhanced the antibiotic action of the encapsulated VCM across all tested microorganisms. The enhanced VCM action is explained with the increased electrostatic adhesion between the ODTAB-coated VCM-loaded shellac NPs and the negatively charged surface of the microbial cell walls which allows local delivery of VCM with a high concentration directly on the cell membrane. This nanocarrier-mediated boost of the antibiotic action may potentially breathe new life into old antibiotics and help to fight off antibiotic resistance by making them more effective.