Oligodynamic Boons of Daptomycin and Noble Metal Nanoparticles Packaged in an Anti-MRSA Topical Gel Formulation
Authors: Chakravarty Ipsita , Kundu Subir 
Published: June 2019

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%.