Nano-antibiotics: Nano Encapsulation of Natural and Synthetic Antimicrobials to Combat Multi Drug Resistant Pathogens

Abstract

Nano-antibiotics: Nano Encapsulation of Natural and Synthetic Antimicrobials to Combat Multi Drug Resistant Pathogens Increasing rates of bacterial resistance has invalidated the utility of even the most potent antibiotics, resulting in mortality due to failure in infection control and high health care costs. Therefore, design, discovery, and delivery of antimicrobial drugs with improved efficacy and avoidance of resistance are highly demanded. Use of nanotechnology in design and delivery of antimicrobial drugs, particularly in overcoming antibioticsresistant pathogens, is considered to be the most promising alternative for this purpose. The present study was designed with the aims to fabricate diverse bio-based nanoparticles (NP), which are non-toxic, biodegradable and biocompatible. Bio-based nanoparticles fabricated from soya lecithin (liposomes), chitosan and hybrid nanoparticles (a mixture of chitosan and β cyclodextrin) were developed and characterized. Natural antimicrobial agents (bacteriocin and essential oils) and synthetic antibiotics were encapsulated in these bio based nano-carrier systems. These nano-delivery systems were characterized by scanning electron microscope (SEM), atomic force microscope (AFM), Fourier transform infrared spectroscopy (FTIR) and Zeta sizer. It was observed that chitosan nano-particles and liposomes were in the size of less than 100 nm whereas the hybrid nano-particles were more than 300 nm in size. The stability of nanoparticles were measured from zeta potential it was concluded that chitosan nano-particles were bearing almost +50 mV zeta potential so were very stable whereas the stability of hybrid nano-particles and liposomes were considered to be compromised. In the first phase of experimentation cefazolin was encapsulated in above mentioned nano-systems and all these nano-systems were tested against multi drug resistant (MDR) Escherichia coli and Methicillin-resistant Staphylococcus aureus. Antibacterial studies confirmed that chitosan and hybrid nano-particles were effectively killing both MDR pathogens. Whereas, liposomes were not effective in killing them. xii However, chitosan was finally selected for further encapsulation of essential oils, nisin and other antibiotics. In the next phase, cefotaxime was encapsulated in chitosan to explore the antibacterial potential in depth by assessing colony forming unit (CFU) and anti-biofilm assay as well. It was determined that the bare chitosan nano-particles could control the growth of pathogens to maximum 48 hours and after that there was a sharp rise in optical density. Anti-biofilm activity confirmed that bare chitosan nano-particles inhibited the bacterial growth by forming agglomerates but they were not effectively combatting biofilm formation and that is the reason bacteria regrow after wards. However, in the case of drug encapsulated chitosan nano-particles the biofilm is totally eradicated. In the third phase, natural anti-microbial agents like essential oils and nisin were also encapsulated in chitosan and they were also found to be effective in killing the MDR pathogens. It is expected that the nano-encapsulation of antimicrobial agents will aid in control of resistance phenomenon in pathogenic microbes.