International Journal of Nanomedicine (Oct 2020)
Synergistic Nanocomposites of Different Antibiotics Coupled with Green Synthesized Chitosan-Based Silver Nanoparticles: Characterization, Antibacterial, in vivo Toxicological and Biodistribution Studies
Abstract
Muhammad Arif Asghar,1 Rabia Ismail Yousuf,1 Muhammad Harris Shoaib,1 Muhammad Asif Asghar,2 Sabah Ansar,3 Mehrukh Zehravi,4 Ahad Abdul Rehman5 1Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi 75270, Pakistan; 2Food and Feed Safety Laboratory, Food and Marine Resources Research Centre, PCSIR Laboratories Complex, Karachi, Sindh 74200, Pakistan; 3Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia; 4Department of Clinical Pharmacy, College of Pharmacy for Girls, Prince Sattam Bin Abdul Aziz University, Al-Kharj 16278, Kingdom of Saudi Arabia; 5Department of Pharmacology, Faculty of Pharmacy, Jinnah Sindh Medical University, Karachi 75510, PakistanCorrespondence: Rabia Ismail Yousuf; Muhammad Harris ShoaibDepartment of Pharmaceutics and Bioavailability and Bioequivalence Research Facility, Faculty of Pharmacy and Pharmaceutical Sciences, University of Karachi, Karachi 75270, PakistanEmail [email protected]; [email protected]: The present study reports chitosan functionalized green synthesized CS-AgNPs, conjugated with amoxicillin (AMX), cefixime (CEF), and levofloxacin (LVX) for safe and enhanced antibacterial activity.Methods: The CS-AgNPs and conjugates CS-AgNPs+AMX CS-AgNPs+CEF, and CS-AgNPs+LVX were characterized by UV–Vis, FTIR, SEM, TEM, EDX spectroscopy. The size distribution and zeta potential were measured using the dynamic light scattering (DLS) technique. The interaction between CS-AgNPs and antibiotic molecules was also investigated using UV–Vis spectroscopy at the concentrations of 5, 50, 500, and 5000 μM for each antibiotic. Antibacterial activity and synergism were assessed by the Fractional Inhibitory Concentration (FIC) index. The mechanism for synergistic activity was investigated by the detection of hydroxyl species based on the chemiluminescence of luminol. The biocompatibility index (BI) was calculated from IC50 using the HeLa cell line. In vivo toxicity and tissue distribution of silver ions were evaluated on Sprague Dawley rats. Physical interactions of antibiotics and significant (P< 0.05) antibacterial activity were observed after loading on CS-AgNPs surfaces.Results: The spherical shape nanocomposites of CS-AgNPs with different antibiotics were prepared with mean size ranges of 80– 120 nm. IC50 of antibiotics-conjugated CS-AgNPs decreased compared to CS-AgNPs. The biocompatibility (BI) index showed that antibiotics-conjugated CS-AgNPs have high antibacterial potential and low toxicity. Highly significant (P< 0.005) increase in the generation of hydroxyl species indicated the radical scavenging mechanism for synergistic activity of CS-AgNPs after combined with different antibiotics. Biochemical analysis and histopathological examinations confirmed low toxicity with minor hepatotoxicity at higher doses. After oral administration, extensive distribution of Ag ion was observed in spleen and liver.Conclusion: The study demonstrates positive attributes of antibiotics-conjugated CS-AgNPs, as a promising antibacterial agent with low toxicity.Keywords: chitosan functionalized silver nanoparticles, antibiotic resistance, synergistic antibacterial activity, in vivo toxicity, tissue distribution
