Oligodynamic Boons of Daptomycin and Noble Metal Nanoparticles Packaged in an Anti-MRSA Topical Gel Formulation

Abstract

Background: Daptomycin is a popular anti-MRSA antibiotic, especially for surgical wound infections. The side-effects of Daptomycin dosage through intravenous administration have prompted the experimental use of topical Daptomycin. Also, combinatorial drug therapy involving noble metal nanoparticles and conventional antibiotics have proved beneficial in the past. The synergistic oligodynamic effect of Daptomycin with nanoparticles for topical application was attempted for the first time in this work. Objectives: The present study was focused on topical gel formulation containing Daptomycin combined with mycogenic gold, silver and bimetallic gold and silver nanoparticles and evaluation of their synergistic antibacterial effect against an MRSA strain. Methods: An efficient approach for fungal growth was discussed wherein the biomass was cultivated under non-limiting conditions, followed by the addition of gold salt, silver salt and bimetallic (Gold and silver) solution. The metal salt reduction efficacy was evaluated using Cyclic Voltammetry. Formation of nanoparticles was observed by visual color changes and confirmed by UV-visible characteristic peaks. The mycosynthesized metallic and bimetallic nanoparticles were characterized by various advanced analytical methods. Further, Daptomycin was combined with nanoparticles in a topical gel formulation. The properties of the topical gels were evaluated and their antimicrobial activity was investigated against an MRSA strain associated with burn infections though disc diffusion method. Results: Formation of nanoparticles was observed by visual color changes and confirmed by UVvisible characteristic peaks. XRD spectra revealed the crystalline nature of nanoparticles whereas TEM confirmed the presence of spherical nanoparticles. The bio fabricated nanoparticles were characterized using ICP-MS, XRD and TEM. The UV-Visible spectrum of the gold, silver, bimetallic nanoparticles showed a characteristic peak at 550 nm, 450 nm, and 480 nm, respectively. ICP-MS of the residual salt concentration depicted more than 75% bioconversion of metal salt to metal nanoparticles. TEM showed the formation of uniform, spherical monometallic nanoparticles. XRD results were in sync with the dynamic light scattering experiments which determined that the gold, silver, bimetallic nanoparticles ranged between 10-20 nm, 5-30 nm, and 20-40 nm respectively and were crystalline in nature with the face centered cubic symmetry. Topical gels combining Daptomycin and nanoparticles were formulated and characterized. The in-vitro drug release studies indicated controlled release of antibiotic from bimetallic nanoparticles and Daptomycin combination in topical gel formulation. The MIC values reduced for the combinatorial drug and the average synergistic antimicrobial effect was 37% and the increase in efficacy of Daptomycin due to the synergistic effect with bimetallic nanoparticles was 43%. Conclusions: Topical gels were formulated using the biologically synthesized gold, silver and bimetallic gold-silver nanoparticles and modern-day antibiotic Daptomycin to combat burn infections. The topical gel formulations showed enhanced antimicrobial activity against methicillin-resistant Staphylococcus aureus at lower MIC values as compared to individual nanoparticle or antibiotic. The best results were obtained with bimetallic nanoparticles in topical gel formulation as it assisted in controlled drug release up to 94.6% and improved antimicrobial effect i.e. 43%.