International Journal of Pharmaceutics 446 (2013) 63–69
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International Journal of Pharmaceutics
jo ur nal homep a ge: www.elsevier.com/locate/ijpharm
Caprolactam-silica network, a strong potentiator of the antimicrobial activity of
kanamycin against Gram-positive and Gram-negative bacterial strains
Georgeta Voicu
a
, Valentina Grumezescu
a,b
, Ecaterina Andronescu
a
, Alexandru Mihai Grumezescu
a,∗
,
Anton Ficai
a
, Denisa Ficai
c
, Cristina Daniela Ghitulica
a
, Irina Gheorghe
d
, Mariana Carmen Chifiriuc
d
a
Department of Science and Engineering of Oxidic Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest 011061,
Romania
b
National Institute for Lasers, Plasma & Radiation Physics, Lasers Department, P.O. Box MG-36, Bucharest-Magurele, Romania
c
Department of Inorganic Chemistry, Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, 011061, Romania
d
Department of Microbiology and Immunology, Faculty of Biology, University of Bucharest 060101, Romania
a r t i c l e i n f o
Article history:
Received 30 November 2012
Received in revised form 31 January 2013
Accepted 1 February 2013
Available online 10 February 2013
Keywords:
MIC
Kanamycin sulfate
Silica
Antimicrobial therapy
Caprolactam
a b s t r a c t
Here, we report the fabrication of a novel -caprolactam-silica (-SiO
2
) network and assessed its
biocompatibility and ability to improve the antimicrobial activity of kanamycin. The results of the quan-
titative antimicrobial assay demonstrate that the obtained -SiO
2
network has efficiently improved the
kanamycin activity on Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 strains, with
a significant decrease of the minimum inhibitory concentration. The -SiO
2
network could be feasibly
obtained and represents an alternative for the design of new antibiotic drug carriers or delivery systems
to control bacterial infections.
© 2013 Elsevier B.V. All rights reserved.
1. Introduction
During the last decades a diversity of polymer based pharma-
ceutical carrier systems have been developed as new means of
controlling temporal or distributional (site-specific) drug delivery,
offering numerous advantages compared to conventionally admin-
istrated drugs in dosage forms, such as improved efficiency and
reduced toxicity (Rosler et al., 2008; Ye et al., 2008; Dhanasingh
et al., 2011; Asgary et al., 2011; Grumezescu et al., 2011a). The ideal
drug delivery system should be inert or biodegradable, biocompat-
ible, mechanically strong, comfortable for the patient, capable of
achieving high drug loading, safe from accidental release, simple to
administer and remove, and easy to fabricate and sterilize (Ye et al.,
2008).
Materials based on silica matrices have been extensively high-
lighted for many biomedical applications, as delivery carriers for
therapeutic agents (Wang et al., 2011). The main advantage of sil-
ica is that it provides a biocompatible, nontoxic surface, with a high
hydrophilicity. It is also quite stable in blood. These particles will
therefore have a prolonged half-life in the blood stream (Yu et al.,
2011; Lin and Haynes, 2010). Silanol groups, Si-OH, and the porosity
∗
Corresponding author. Tel.: +40 765349326.
E-mail address: grumezescu@yahoo.com (A.M. Grumezescu).
of silica network play an important role in controlling the release
of the therapeutic agents (Pon-On et al., 2011). Many studies have
been reported with drug delivery from silica materials and it has
been shown that silica is able to store and gradually release ther-
apeutic agents (Meseguer-Olmo et al., 2006; Florea et al., 2012).
In many diseases the administration of a drug is only required at
specific time intervals in which constant drug levels could lead to
adverse effects (Bikram et al., 2007).
Aminoglycosides are clinically important antibiotics to treat
infectious diseases caused by Gram-positive and Gram-negative
bacteria. These drugs bind to the decoding region of ribosome,
inducing codon misreading, inhibiting translocation, and eventu-
ally leading to cell death (Chen et al., 2009; Hermann, 2000).
Kanamycin (sulfate), (2-(aminomethyl)-6-[4,6-diamino-3-
[4-amino-3,5-dihydroxy-6-(hydroxymethyl)tetrahydropyran-2-
yl]oxy-2-hydroxy-cyclohexoxy], tetrahydropyran-3,4,5-triol) is
an aminoglycoside antibiotic solely produced by fermentation
using certain strains of Streptomyces kanamyceticus (Megoulas
and Koupparis, 2005). It is widely administrated as a second line
antibiotic in the form of injection and capsules. Like most of
aminoglycosides, dose dependent side effects of ototoxicity and
nephrotoxicity have been observed (Gennaro, 1985).
Previous studies have shown that biodegradable silica xerogel
could be an efficient carrier of gentamycin antibiotic, the amino-
glycoside molecules entrapped in the sol-gel matrix remaining in
0378-5173/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ijpharm.2013.02.011