Drug resistance is a global health challenge with thousands
of
deaths annually caused by bacterial multidrug resistance (MDR). Efforts
to develop new antibacterial molecules do not meet the mounting needs
imposed by the evolution of MDR. An alternative approach to overcome
this challenge is developing targeted formulations that can enhance
the therapeutic efficiency and limit side effects. In this aspect,
vancomycin is a potent antibacterial agent that has inherent bacterial
targeting properties by binding to the D-Ala-D-Ala moiety of the bacterial
peptidoglycan. However, the use of vancomycin is associated with serious
side effects that limit its clinical use. Herein, we report the development
of vancomycin-conjugated magnetic nanoparticles using a simple conjugation
method for targeted antibacterial activity. The nanoparticles were
synthesized using a multistep process that starts by coating the nanoparticles
with a silica layer, followed by binding an amide linker and then
binding the vancomycin glycopeptide. The developed vancomycin-conjugated
magnetic nanoparticles were observed to exhibit a spherical morphology
and a particle size of 16.3 ± 2.6 nm, with a silica coating thickness
of 5 nm and a total coating thickness of 8 nm. The vancomycin conjugation
efficiency on the nanoparticles was measured spectrophotometrically
to be 25.1%. Additionally, the developed formulation retained the
magnetic activity of the nanoparticles, where it showed a saturation
magnetization value of 51 emu/g, compared to 60 emu/g for bare magnetic
nanoparticles. The in vitro cell biocompatibility demonstrated improved
safety where vancomycin-conjugated nanoparticles showed IC
50
of 183.43 μg/mL, compared to a much lower value of 54.11 μg/mL
for free vancomycin. While the antibacterial studies showed a comparable
activity of the developed formulation, the minimum inhibitory concentration
was 25 μg/mL, compared to 20 μg/mL for free vancomycin.
Accordingly, the reported formulation can be used as a platform for
the targeted and efficient delivery of other drugs.