We report a strong enhancement in the antimicrobial action of berberine and chlorhexidine encapsulated into polyacrylic acid-based nanogels followed by further surface functionalisation with a cationic polyelectrolyte (PDAC) . Due to the highly developed surface area, the nanogel carrier amplifies the contact of berberine and chlorhexidine with microbial cells and increases its antimicrobial efficiency. We show that such cationic nanogel carriers of berberine can adhere directly to the cell membranes and maintain a very high concentration of berberine directly on the cell surface. We demonstrated that the antimicrobial action of the PDAC coated nanogel loaded with berberine and chlorhexidine on E. coli, yeast, and C. reinhardtii is much higher than that of the equivalent solution of both free berberine or free chlorhexidine due to the electrostatic adhesion between the positively charged nanogel particles and the cell membranes. Our results also showed a marked increase in their antimicrobial action at shorter incubation times compared to the non-coated nanogel particles loaded with the same antimicrobial agent under identical conditions. We attribute this boost in the antimicrobial effect of these cationic nanocarriers to their accumulation on the cell membranes which sustains a high concentration of released berberine or chlorhexidine causing cell death within much shorter incubation times. This study can provide a blueprint for boosting the action of other cationic antimicrobial agents by encapsulating them into nanogel carriers functionalised with a cationic surface layer. This nanotechnology-based approach could lead to the development of more effective wound dressings, disinfecting agents, antimicrobial surfaces, and antiseptic and antialgal/antibiofouling formulations.
 M.J. Al-Awady, G.M. Greenway, V.N. Paunov, J. Mater. Chem. B, 2017, 5, 7885-7897.