Nazarbayev University, Kazakhstan
Prof Vesselin Paunov received his PhD in Physical Chemistry in 1997 from the University of Sofia, Bulgaria. He worked as a visiting researcher at the Universities of Patras, Greece, and Erlangen, Germany and as a postdoctoral research fellow at the Universities of Hull, UK and Delaware, USA. In 2000 he took an academic post at the University of Hull, UK where he became a Professor of Physical Chemistry and Advanced Materials in 2013. At present he is a Professor and Chair of Chemistry at Nazarbayev University, Astana, Kazakhstan. His current research interests include formulation science, microencapsulation, triggered release of actives, antimicrobial nanoparticles, bioimprint-cell shape recognition and 3D cell culture. He has published over 185 research articles that have received more 11000 citations.
Nanotechnologies in the fight against antimicrobial resistance
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 [1-4], nanogels  and nanocarriers of biocompatible materials [6-7] 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 [6,7] by encapsulating them into surface functionalized nanocarriers for more effective antimicrobial formulations against resistant bacteria. Strong amplification of the antimicrobial action of vancomycin (VCM) was reported when it was encapsulated in shellac nanoparticles with dual surface functionalization. The enhanced VCM action is due to the increased electrostatic adhesion between the ODTAB-coated VCM-loaded shellac NPs and the negatively charged microbial cell walls which allows local delivery of a high concentration of VCM. 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 and tested a novel type of formulation of copper oxide (CuONPs) nanoparticles which have been functionalized with (3-Glycidyloxypropyl)trimethoxysilane (GLYMO) to allow further covalent coupling of 4-hydroxyphenylboronic acid (4-HPBA). As the boronic acid groups on the surface of CuONPs/GLYMO/4-HPBA can form reversible covalent bonds with the diols groups of glycoproteins that are expressed on the bacterial cell surface, they can strongly bind to the bacterial cells walls resulting in a very strong enhancement of their antibacterial action which is not based on electrostatic adhesion [1-3]. Such nanotechnology-based approaches may enhance the effectiveness of a wide variety of existing antibiotics, offering a potentially new mechanism to overcome antibiotic resistance. 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 nanotechnology-based approach could lead to the development of more effective wound dressings, disinfecting agents, antimicrobial surfaces and smart antiseptic formulations.
 A. F. Halbus, T.S. Horozov and V.N. Paunov, ACS Appl. Mater. Interf., 2019, 11, 12232–12243.
 A. F. Halbus, T.S. Horozov and V.N. Paunov, Nanoscale Adv., 2019, 1, 2323–2336.
 A.F. Halbus, T.S. Horozov and V.N. Paunov, ACS Appl. Mater. Interf., 2019, 11, 38519−38530.
 A. Richter, J.S. Brown, B. Bharti, A. Wang, A., S. Gangwal, K. Houck, E.A. Cohen Hubal, V.N. Paunov, et al., Nature Nanotechnology, 2015, 10, 817-823.
 P.J. Weldrick, S. Iveson, M.J. Hardman and V.N. Paunov, Nanoscale, 2019, 11 10472-10485.
 S.S.M, Al-Obaidy, A.F. Halbus, G.M. Greenway and V.N. Paunov, J. Mater. Chem. B, 2019, 7, 3119-3133.
 S.S.M, Al-Obaidy, G.M. Greenway and V.N. Paunov, Nanoscale Adv., 1, 2019, 858–872.