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University Politehnica of Bucharest, Faculty of Applied Chemistry and Materials Science, Gh. Polizu 1, Bucharest, Romania
University of Bucharest, Faculty of Biology, Department of Microbiology and Immunology, Intr. Portocalelor 1-3, Bucharest, Romania
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Article history:
Received 15 August 2013
Received in revised form 3 November 2013
Accepted 18 November 2013
Available online xxx
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Keywords:
Zinc oxide
Chitosan
Gentamicin
Controlled release
Improved wound dressing
Antimicrobial effect
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1. Introduction
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Freshly prepared ZnO nanoparticles were incorporated into a chitosan solution in weight ratios ranging
from 1:1 to 12:1. Starting from the ratio of 3:1 the chitosan solution was transformed into a gel with a high
consistency, which incorporates 15 mL water for only 0.1 g solid substance. The powders obtained after
drying the gel were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and
thermal analysis (TG-DSC). The electronic (UVvis), infrared (FTIR) and photoluminescence (PL) spectra
were also recorded. ZnO particles were coated with gentamicin and incorporated into the chitosan matrix,
to yield a ZnO/gentamicinchitosan gel. The release rate of gentamicin was monitored photometrically.
This ZnO/gentamicinchitosan gel proved great antimicrobial properties, inhibiting Staphylococcus aureus
and Pseudomonas aeruginosa growth in both planktonic and surface-attached conditions. The results
indicate that the obtained composite can be used in cutaneous healing for developing improved wound
dressings, which combine the antibacterial activity of all three components with the controlled release
of the antibiotic. This wound dressing maintains a moist environment at the wound interface, providing
a cooling sensation and soothing effect, while slowly releasing the antibiotic. The system is fully scalable
to any other soluble drug, as the entire solution remains trapped in the ZnOchitosan gel.
2013 Published by Elsevier B.V.
Grumezescu et al., 2012a,b; Sogias et al., 2012). One of the applications that received much attention in the last years is related
to the potential uses of chitosan in the process of wound healing (Archana et al., 2013; Ribeiro et al., 2013; Wijekoon et al.,
2013).
Incorporation of zinc oxide nanoparticles into chitosan comes
as one of natural solutions to develop new bandages for wound
dressing (Kumar et al., 2012a,b), as the antibacterial activity of the
composite ZnOchitosan is also well documented in the literature
(El Shafei and Abou-Okeil, 2011; Liu and Kim, 2012; Perelshtein
et al., 2013).
Gentamicin belongs to the class of aminoglycoside antibiotics,
widely used to treat many types of serious infections, particularly
those caused by Gram-negative bacteria. It is usually used to treat
skin infections, soft tissues and bone infection, and also extreme
burns-associated infections (Builders et al., 2013; Manjunatha et al.,
2010). Rapid debridement of burn wounds and the application of
effective topical and systemic antimicrobial agents can improve the
efcacy of burn therapy (Sun et al., 2012).
Many types of nosocomial pathogens are drug-resistant and
patients infected with these drug-resistant pathogens are at a high
risk. As different bacterial strains become increasingly resistant
Please cite this article in press as: Vasile, B.S., et al., Synthesis and characterization of a novel controlled release zinc oxide/gentamicinchitosan
composite with potential applications in wounds care. Int J Pharmaceut (2013), http://dx.doi.org/10.1016/j.ijpharm.2013.11.035
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Fig. 1. The ZnOchitosan gels. On top row (from left to right) synthesis with ZnO:chitosan ratio of 1:1; 2:1; 3:1; 4:1; 5:1 and 6:1. On bottom row, the ZnOchitosan gels have
high consistency starting with ZnO:chitosan ratio 3:1.
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Please cite this article in press as: Vasile, B.S., et al., Synthesis and characterization of a novel controlled release zinc oxide/gentamicinchitosan
composite with potential applications in wounds care. Int J Pharmaceut (2013), http://dx.doi.org/10.1016/j.ijpharm.2013.11.035
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Fig. 2. (a) ZnOchitosan gel (12:1) cut in shapes; (b) close view of a ZnOchitosan cube; and (c) ZnOchitosan cube after 3 months in water.
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0.89
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Fig. 3. XRD pattern of the ZnOchitosan nanopowders 6:1 and 12:1 and
ZnO/gentamicinchitosan nanopowder 12:2:1.
Please cite this article in press as: Vasile, B.S., et al., Synthesis and characterization of a novel controlled release zinc oxide/gentamicinchitosan
composite with potential applications in wounds care. Int J Pharmaceut (2013), http://dx.doi.org/10.1016/j.ijpharm.2013.11.035
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Fig. 4. TEM and HRTEM images of ZnO polyhedral shaped particles and SAED pattern of planes for hexagonal ZnO [ASTM 80-0075].
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Please cite this article in press as: Vasile, B.S., et al., Synthesis and characterization of a novel controlled release zinc oxide/gentamicinchitosan
composite with potential applications in wounds care. Int J Pharmaceut (2013), http://dx.doi.org/10.1016/j.ijpharm.2013.11.035
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Fig. 5. TEM and HRTEM images of ZnOchitosan (12:1) dry nanopowder and SAED pattern of planes for hexagonal ZnO [ASTM 80-0075].
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Please cite this article in press as: Vasile, B.S., et al., Synthesis and characterization of a novel controlled release zinc oxide/gentamicinchitosan
composite with potential applications in wounds care. Int J Pharmaceut (2013), http://dx.doi.org/10.1016/j.ijpharm.2013.11.035
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for ZnO/gentamicin and over thirty times higher than the one
corresponding to the bare ZnO nanoparticles. Because surface optical emission efciency can increase over tenfold as roughness
decreases to unit cell dimensions (Doutt et al., 2009), we can
attribute this high intensity of NBE to the smoothing of the nanoparticles surface during incorporation into the chitosan solution.
Such high intensity emission band can be further used in other
medical application, such as photodiagnosis or biosensing (Zhao
et al., 2013).
The electronic spectra recorded for the uncoated and gentamicin coated ZnO powder is presented in Fig. 8. The calculated band
gap for ZnO is 3.36 eV, in good agreement with the literature. The
absorbance of the ZnOchitosan nanopowder is slightly higher than
that of uncoated ZnO, in the visible region, the layer of chitosan
contributing to the light absorption. For ZnO/gentamicinchitosan
the absorbance in visible region is further increased as the organic
layer contains two components. As the spectrum is recorded in
reectance mode, the photons that are not absorbed by ZnO must
travel twice through the gentamicin and chitosan layer, yielding a
higher absorbance. The maximum absorbance for all the samples
is at 363 nm.
thermal
analysis
of
ZnOchitosan
and
The
ZnO/gentamicinchitosan nanopowders (Fig. 9) are similar up to
(a)
ZnO;
(b)
ZnOchitosan);
(c)
Please cite this article in press as: Vasile, B.S., et al., Synthesis and characterization of a novel controlled release zinc oxide/gentamicinchitosan
composite with potential applications in wounds care. Int J Pharmaceut (2013), http://dx.doi.org/10.1016/j.ijpharm.2013.11.035
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Fig. 10. The gentamicin release from the ZnO/gentamicin nanopowder and
ZnO/gentamicinchitosan gel.
Fig. 11. The proposed models of (a) ZnO nanoparticleschitosan interaction; and
(b) ZnOchitosan gel structure.
Please cite this article in press as: Vasile, B.S., et al., Synthesis and characterization of a novel controlled release zinc oxide/gentamicinchitosan
composite with potential applications in wounds care. Int J Pharmaceut (2013), http://dx.doi.org/10.1016/j.ijpharm.2013.11.035
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Fig. 14. Graphic representation of MICs obtained after growing S. aureus and
P. aeruginosa in the presence of diferent concentrations of gentamicin and
ZnO/gentamicinchitosan.
4. Conclusions
In this paper we describe an easy method to incorporate ZnO
nanoparticles into a chitosan solution at a weight ratio up to 12:1.
The obtained gel has proved a high water content (99.33% weight),
but also a high consistency, maintaining its shape after cutting.
Furthermore, this product is stable up to three days in laboratory atmosphere, and over three months if immersed in water.
The incorporation of gentamicin loaded ZnO nanoparticles in chitosan solution yields a three-component gel, with a slow release
rate of the drug. As all three components have antibacterial activity, a synergic action was expected. The results proved a four-fold
MIC reduction for S. aureus and a two-fold reduction of MIC for P.
aeruginosa. The gel can be used in topic applications that requires
a large spectrum antibacterial activity, namely as a bandage for
wound dressing. The high water content help in maintaining a
moist environment at the wound interface, providing a cooling
sensation and soothing effect, much like aloe vera base gel, while
slowly releasing the antibiotic. Most important, the system is fully
scalable to any other soluble drug, as the entire solution remains
trapped in the ZnOchitosan gel.
In addition, for the ZnOchitosan nanopowder we report here
an unusual high intensity for the UV emission band, property that
can be further used in various medical elds like photodiagnosis or
biosensing.
Acknowledgment
Authors recognize nancial support from the European Social
Fund through POSDRU/89/1.5/S/54785 project: Postdoctoral Program for Advanced Research in the Field of Nanomaterials.
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Please cite this article in press as: Vasile, B.S., et al., Synthesis and characterization of a novel controlled release zinc oxide/gentamicinchitosan
composite with potential applications in wounds care. Int J Pharmaceut (2013), http://dx.doi.org/10.1016/j.ijpharm.2013.11.035
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Please cite this article in press as: Vasile, B.S., et al., Synthesis and characterization of a novel controlled release zinc oxide/gentamicinchitosan
composite with potential applications in wounds care. Int J Pharmaceut (2013), http://dx.doi.org/10.1016/j.ijpharm.2013.11.035
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