Tetracycline Water Soluble Formulations with Enhanced Antimicrobial Activity

• Main Authors: A. Meretoudi, C. N. Banti, P. Siafarika, A. G. Kalampounias, S. K. Hadjikakou
• Format: Article
• Language: English
• Published: MDPI AG 2020-11-01
• Series: Antibiotics
• Subjects: biological inorganic chemistry; antibiotic; tetracycline; micelles; antimicrobial activity; toxicity
• Online Access: https://www.mdpi.com/2079-6382/9/12/845
• ISSN: 2079-6382

The negligible water solubility of tetracycline (<b>TC</b>), a well-known antibiotic of clinical use, is the major disadvantage for its oral administration. With the aim to improve the water solubility of <b>TC,</b> the micelles of formulae <b>SLS@TC</b> and <b>CTAB@TC </b>(<b>SLS</b> = sodium lauryl sulphate and <b>CTAB</b> = cetrimonium bromide) were synthesized. The micelles <b>SLS@TC</b> and <b>CTAB@TC</b> were characterized by melting point (m.p.), thermogravimetric differential thermal analysis (TG-DTA), differential scanning calorimetry (DTG/DSC), attenuated total reflection spectroscopy (FT-IR-ATR), ultra-violet visible (UV/vis) spectroscopy, proton nucleus magnetic resonance (¹H-NMR) spectroscopy, and the ultrasonically-induced biregringence technique. The antimicrobial activity of <b>SLS@TC</b> and <b>CTAB@TC</b> was evaluated, by means of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and inhibition zone (IZ), against the Gram negative bacterial strains <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) and <i>Escherichia coli (E. coli) </i>and the Gram positive ones of the genus <i>of Staphylococcus epidermidis</i> (S. <i>epidermidis</i>) and <i>Staphylococcus aureus</i> (<i>S. aureus</i>). Generally, both micelles show better activity than that of <b>TC</b> against the microbial strains tested. Thus, the MIC value of <b>CTAB@TC</b> is 550-fold higher than that of free <b>TC</b> against <i>S. epidermidis</i>. Despite the stronger activity of <b>CTAB@TC</b> than <b>SLS@TC</b> against both Gram negative and Gram positive microbes, <b>SLS@TC</b> is classified as a bactericidal agent (in that it eliminates 99.9% of the microbes), in contrast to <b>CTAB@TC</b>, which is bacteriostatic one (inhibits, but does not kill the organisms). The toxicity of <b>SLS@TC</b> and <b>CTAB@TC</b> was evaluated against human corneal eukaryotic cells (HCECs). Moreover, <b>SLS@TC</b> and <b>CTAB@TC</b> exhibit low in vivo toxicity against <i>Artemia salina</i>, even at concentrations up to threefold higher than those of their MIC^max. Therefore, <b>SLS@TC</b> and <b>CTAB@TC</b> can be candidates for the development of new antibiotics.