TY - JOUR
T1 - TXA497 as a topical antibacterial agent
T2 - Comparative antistaphylococcal, skin deposition, and skin permeation studies with mupirocin
AU - Dorrani, Mania
AU - Kaul, Malvika
AU - Parhi, Ajit
AU - Lavoie, Edmond J.
AU - Pilch, Daniel S.
AU - Michniak-Kohn, Bozena
N1 - Funding Information:
This study was supported in part by research agreements between TAXIS Pharmaceuticals, Inc., and both Rutgers Robert Wood Johnson Medical School (D.S.P) and Rutgers Ernest Mario School of Pharmacy (E.J.L.) . We are indebted to Dr. Glenn W. Kaatz (John D. Dingell VA Medical Center, Detroit, MI) and Dr. George M. Eliopoulos (Beth Israel Deaconess Medical Center; Boston, MA) for providing us with the S. aureus 8325-4 and Mu3 strains, respectively.
Publisher Copyright:
© 2014 Elsevier B.V. All rights reserved.
PY - 2014/12/10
Y1 - 2014/12/10
N2 - TXA497 is representative of a new class of guanidinomethyl biaryl compounds that exhibit potent bactericidal behavior against methicillin-resistant Staphylococcus aureus (MRSA). In this study, we compared the anti-staphylococcal, skin deposition, and skin permeation properties of TXA497 and the topical anti-MRSA antibiotic mupirocin. The results of minimum inhibitory concentration (MIC) assays revealed that TXA497 retains potent activity against MRSA that is highly resistant to mupirocin. Using Franz diffusion cells, compound deposition into human cadaver skin was evaluated, and the results showed the skin deposition of TXA497 to be significantly greater than that of mupirocin. Moreover, unlike mupirocin, TXA497 does not pass through the entire skin layer, suggesting a minimal potential for the systemic absorption of the compound upon topical administration. Additionally, antibacterial concentrations of TXA497 showed no significant toxicity to primary human keratinocytes. Given the rising levels of mupirocin resistance among MRSA populations, our results are significant in that they highlight TXA497 as a potentially useful alternative therapy for treating MRSA skin infections that are resistant to mupirocin.
AB - TXA497 is representative of a new class of guanidinomethyl biaryl compounds that exhibit potent bactericidal behavior against methicillin-resistant Staphylococcus aureus (MRSA). In this study, we compared the anti-staphylococcal, skin deposition, and skin permeation properties of TXA497 and the topical anti-MRSA antibiotic mupirocin. The results of minimum inhibitory concentration (MIC) assays revealed that TXA497 retains potent activity against MRSA that is highly resistant to mupirocin. Using Franz diffusion cells, compound deposition into human cadaver skin was evaluated, and the results showed the skin deposition of TXA497 to be significantly greater than that of mupirocin. Moreover, unlike mupirocin, TXA497 does not pass through the entire skin layer, suggesting a minimal potential for the systemic absorption of the compound upon topical administration. Additionally, antibacterial concentrations of TXA497 showed no significant toxicity to primary human keratinocytes. Given the rising levels of mupirocin resistance among MRSA populations, our results are significant in that they highlight TXA497 as a potentially useful alternative therapy for treating MRSA skin infections that are resistant to mupirocin.
KW - MRSA
KW - MSSA
KW - Mupirocin
KW - Skin permeation
KW - TXA497
KW - Topical anti-bacterial
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U2 - 10.1016/j.ijpharm.2014.09.033
DO - 10.1016/j.ijpharm.2014.09.033
M3 - Article
C2 - 25263100
AN - SCOPUS:84907978487
SN - 0378-5173
VL - 476
SP - 199
EP - 204
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1
ER -