By Dr. Megha Agrawal, Dr. Shyamasri Biswas, Dr.

Kim Van Vliet, Contributing Editors

Vacuum Deposited Antimicrobials:

A Pharmaceutical Biotechnology
Route to Battle Infectious Diseases

igh-vacuum and ultra-high-vacuum technology based deposition and coating processes are
considered effective methods to prepare
antimicrobial products. Development of
advanced antimicrobials with superior
actions is currently an important area of
biotechnology R&D in the drug and pharmaceutical industry. Antimicrobials or antibacterial agents have many applications
in the biomedical sector to protect human
health such as prevention of surgical site
infections, nasal infections or prevention
of bacterial infections of other hospitals
and medical procedures where resistant
bacteria are prevalent. Antimicrobials and
antibacterial agents were created to prevent the spread of infections in hospitals.
Today, there are approximately over 2000
products that have antimicrobial agents
in them which are commonly used by
consumers. By using more antimicrobial
agents, the bacteria are exposed to these
agents and most get eliminated. However, through a process of selection, a small
fraction of the bacteria can mutate and develop resistance to the treatment.
In the past few decades, the emergence
of an increasing number of bacterial
strains has happened, but due to mutations, a majority of them have become
drug resistant. As a result, the antimicro-

bials currently in use are under increased

scrutiny. Due to the tough legislation to
regulate such antimicrobial agents, new
antimicrobials are needed, particularly for
hospitals and medical procedures, where
resistant bacterial are prevalent. Vacuum
technology offers hope to develop new
types of antimicrobials that are more effective to combat infectious diseases.
Several examples of vacuum deposition
process based development of antibacterials have been reported. Notably, the antibacterial effect of thin titaniumcopper
(TiCu) films combined with sufficient
growth of human osteoblastic cells were
reported in a recent paper. Three different plasma-assisted magnetron sputtering
methods comprising direct current magnetron sputtering (dc-MS), dual magnetron sputtering (dual-MS) and dual high
power impulse magnetron sputtering
(dual-HiPIMS) were employed to prepare
thin TiCu films. It was argued that the
antimicrobial effect was caused by copper
released from the metallic TiCu films,
which was measured by atomic absorption spectroscopy (AAS). The researchers
investigated In-vitro planktonic growth on
TiCu surfaces for Staphylococcus epidermidis and S. aureus that demonstrated the killing of both bacteria using the
TiCu films prepared by dual-HiPIMS

Vacuum Technology & Coating December 2015 www.vtcmag.com 

technique. The authors concluded that the

cytotoxic effect combined with growth of
osteoblastic cells could be used in joint replacement surgery to reduce the possibility of infection and to increase adoption of
the implants [1].
Pulsed laser deposition was applied to
prepare antimicrobial silver coating on
Ormocer microneedles [2]. Microneedles
are used for transdermal delivery of protein- and nucleic acid-based pharmacologic agents. However, the most common
problem with using microneedle is the
generated pores that may allow microorganisms to penetrate the stratum corneum layer of the epidermis. This causes
local or systemic infection. In their work,
the researchers fabricated microneedles
with antimicrobial functionality using
a combination of two-photon polymerization-micromolding and pulsed laser
deposition. The researchers demonstrated the antibacterial activity of the silver-coated organically modified ceramic
(Ormocer) microneedles (Figure 1) using an agar diffusion assay. The authors
observed that the human epidermal keratinocyte viability on the Ormocer surfaces
coated with silver was similar to that on
uncoated Ormocer surfaces. It was concluded that coating microneedles with
silver thin films using pulsed laser depo1

Figure 1. Scanning electron micrographs of (a) a SR 259 polyethylene glycol dimethacrylate microneedle array serving as a master structure in
the two photon polymerization-micromolding process. (b) a silver-coated Ormocer microneedle array fabricated using a combination of two
photon polymerization-micromolding and pulsed laser deposition [Source: Gittard SD et. al., Biofabrication. 2009 Dec;1(4):041001].

sition can be a useful and novel approach

for creating microneedles with antimicrobial functionality [2].
In another work using pulsed laser
deposition, biopolymer-antibiotic films
were fabricated with antimicrobial activity. The researchers reported fabrication
of two polymer-drug composite thin film
systems using matrix assisted pulsed laser
evaporation (MAPLE) method. They employed a pulsed KrF excimer laser source
( = 248 nm, = 25 ns, = 10 Hz) that
was used to deposit composite thin films
of poly(D,L-lactide) (PDLLA) containing several gentamicin concentrations.
The researchers employed Fourier Transform Infrared FTIR spectroscopy and
they demonstrated that MAPLE-transferred materials exhibited chemical
structures similar to materials prepared
by drop cast method. The authors tested
the activity of PDLLA-gentamicin composite thin films against Staphylococcus
aureus bacteria using a drop testing method. The influence of drug concentration
on microbial viability was also assessed.
Their studies indicated that polymer-drug
composite thin films prepared by MAPLE may be used to impart antimicrobial
activity to implants, medical devices, and
other contact surfaces [3].
Researchers investigated the antibacterial properties of CuCrO2 thin film surfaces against Escherichia coli (E. coli)
bacteria. Single-phase delafossite type
2

copper-chromium oxide (CuCrO2) thin

films were prepared on glass substrate
by radio-frequency (RF) magnetron sputtering [4]. In another work, novel duplex
silver films, exhibiting antimicrobial
behavior, were produced by magnetron
sputtering [5]. For long-term and permanent implant fixations, prevention of bacterial invasion on biomedical implants is
a fundamental requirement. Prevention of
initial bacterial adherence on metallic implants is an important concern to avoid extracellular matrix (biofilm) secretion from
bacteria that is resistant to antibacterial
agents. In this regard, antibacterial effects
of silverzirconia composite coatings using pulsed laser deposition onto 316L SS
for bio implants were investigated [6].
Figure 2 shows epifluorescence microscopy images of ZrO2 and AgZrO2
composite coated 316L SS. In principle,
live cells exhibited orange fluorescence
and dead cells exhibited green color due
to the interaction of AO with cellular
RNA. Bacterial inoculated ZrO2 coatings demonstrated green fluorescence for
E.coli bacteria and orange color fluorescence for S.aureus. The researchers concluded that ZrO2 coating showed bacterial
activity against E.coli but failed to express
the bactericidal nature against S.aureus.
Whereas, in the case of AgZrO2 composite coatings, both E.coli and S.aureus
showed green fluorescence that indicated
dead cells [6].

vtcmag@vtcmag.com 

Ag2O-coated HDPE antimicrobial films

were prepared through vacuum evaporation technique via depositing Ag2O on
the substrate of high density polyethylene
(HDPE) films pretreated by ion bombardment. The Ag2O-coated HDPE films
exhibited strong antibacterial activity
for both gram-negative bacteria (E. coli)
and gram-positive bacteria (S. aureus)
[7]. Researchers developed a special low
temperature (70C) magnetron deposition
process for the deposition of antimicrobial coatings on thermally sensitive polymeric substrates. This low temperature
deposition was achieved by combining
magnetron sputtering with a neutral atom
beam plasma source [8] (Figure 3). The
bacterial adhesion and bactericidal effects
of the coated polymers was investigated
using Staphylococcus epidermidis and the
cytotoxicity using fibroblast cells. Up to a
3 log reduction in bacterial adhesion was
achieved for silver antimicrobial coatings
on polyurethane, which did not exhibit cytotoxicity [8].
Concluding Remarks
In summary, the development of new
antimicrobial surfaces are needed, particularly with the number of bacterial strains
that are resistant to current disinfection
methods in hospitals and surgical suites.
Vacuum technology based deposition and
coating methods have been proven to be

December 2015 Vacuum Technology & Coating

Figure 2. Epifluorescence microscopy images of ZrO2 (a) E.Coli and (b) S.aureus and AgZrO2 composite coatings (c) E.Coli and (d) S.aureus
[Source: G. Pradhaban et. al., Prog Biomater (2014) 3:123130].

extremely versatile and useful to fabricate

and develop advanced antimicrobial thin
films. Infectious diseases can be prevented by new innovations in vacuum process-

ing techniques that are required to develop

and optimize bio-functional and clinically
important antimicrobials or antibacterial
agents for advanced medical applications.

References for Further Reading

1. V. Stranak et. al. Materials Science and Engineering: C, 31, 1512 (2011).
2. Gittard SD, Narayan RJ, Jin C, Ovsianikov
A, Chichkov BN, Monteiro-Riviere NA,
Stafslien S, Chisholm B. Biofabrication
2009 Dec;1(4):041001. doi: 10.1088/17585082/1/4/041001.
3. Cristescu, R. et. al. Applied Surface Science, Volume 278, p. 211-213 (2013).
4. 
Te-Wei Chiu et. al. Vacuum, 87, 174
(2013).
5. S.B. Sant, K.S. Gill & R.E. Burrell, Philosophical Magazine Letters, 80, 249 (2000).
6. G. Pradhaban et. al., Prog Biomater (2014)
3:123130.
7. 
Ya-Na Li & Shu-Cai Li, Polymer-Plastics Technology and Engineering, 49, 725
(2010).
8. D.P. Dowling et al., Thin Solid Films, 602,
398 (2001).

Figure 3. Schematic diagram of the magnetron sputtering/atom beam deposition system for producing antimicrobial coatings [Source: D.P. Dowling et al., Thin Solid Films, 602, 398 (2001)].
Vacuum Technology & Coating December 2015 www.vtcmag.com