Hosts: Prof. Himanshu Mishra & Dr. Ivan Uriev Vakarelski
Multidrug-resistant pathogens are prevalent in chronic wounds. There is an urgent need to develop novel antimicrobials and formulation strategies that can overcome antibiotic resistance, and provide a safe alternative to traditional antibiotics. In this lecture, I will discuss how metal or metal oxide nanoparticles, nanogels and nanocarriers of biocompatible materials have been increasingly explored as efficient antimicrobials themselves as well as delivery platforms for enhancing the effectiveness of existing antibiotics. I will also focus on several examples of these nanocarrier-platforms that were recently developed in my research group. We developed a novel functionalized polyacrylic copolymer nanogel carrier for two cationic antibiotics, tetracycline and lincomycin hydrochloride, which can overcome antibiotic resistance. These nanogels can encapsulate cationic antimicrobials and act as a drug delivery system when functionalized with a biocompatible cationic polyelectrolyte, bPEI. Our data reveal that bPEI-coated nanogels with encapsulated tetracycline or lincomycin displayed super-enhanced antimicrobial performance against selected wound-derived bacteria, including strains highly resistant to the free antibiotic in solution. Additionally, the nanocarrier-based antibiotics showed no detectable cytotoxic effect against human keratinocytes. We attribute the increase in antimicrobial activity of the bPEI-functionalized antibiotic-loaded nanogel carriers to their electrostatic adhesion to the microbial cell wall, which delivers very high local antibiotic concentration and overwhelms their efflux pumps. We applied this strategy for boosting the action of other cationic antimicrobial agents by encapsulating them into surface functionalized nanocarriers for more effective antimicrobial formulations against resistant bacteria. Strong amplification of the antimicrobial action of vancomycin was reported when it was encapsulated in shellac nanoparticles with cationic surface functionalization. Our results can provide a blueprint for boosting the action of other cationic antimicrobial agents by encapsulating them into nanogel carriers functionalized with a cationic surface layer. This approach may breathe new life into a wide variety of existing antibiotics, offering a potentially new mechanism to overcome antibiotic resistance. We also developed self-grafting nanocarriers that bind covalently to bacteria and enhance their antibacterial action. This nanotechnology-based approach could lead to the development of more effective wound dressings, disinfecting agents, antimicrobial surfaces and smart antiseptic formulations.
Vesselin Paunov is Professor of Physical Chemistry and Advanced Materials at the Department of Chemistry and Biochemistry at the University of Hull, UK. He received his PhD in Physical Chemistry from the University of Sofia, Bulgaria, where he studied the lateral capillary interactions between colloid particles adsorbed at liquid surfaces. During his PhD studies he also specialized at the Chemical Engineering Department of the University of Partas, Greece, and at the Institute of Fluid Mechanics at the University of Erlangen, Germany. In 1997 he was awarded NATO/Royal Society Postdoctoral Fellowship at the Department of Chemistry of the University of Hull, UK. In 1998, he moved to the USA as a Post-Doctoral Fellow at the Chemical Engineering Department of the University of Delaware. In 2000 he was appointed as a lecturer in Physical Chemistry at the University of Hull, UK and was promoted to professor in 2013. Prof Paunov does highly interdisciplinary research in the areas of colloids, nanoscience and biomaterials. He has published over 160 scientific papers in international journals and is a co-inventor of 13 patents (google scholar). Prof Paunov has given over 120 invited and conference presentations. His present research interests include formulation science, smart materials, hydrogels, capillary suspensions, microencapsulation, stimulus triggered release of actives, tissue engineering, whole cell biosensors, cell bioimprinting and antimicrobial nanotechnologies (www.paunovgroup.org).