Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08855, USA; Center for Dermal Research, Life Sciences Building, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Department of Pharmacology, Rutgers Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854-5635, USA.
Int J Pharm. 2014 Dec 10;476(1-2):199-204. doi: 10.1016/j.ijpharm.2014.09.033. Epub 2014 Sep 26.
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.
TXA497 是一种新型胍基甲基联苯化合物，对耐甲氧西林金黄色葡萄球菌 (MRSA) 具有很强的杀菌作用。在这项研究中，我们比较了 TXA497 和局部抗 MRSA 抗生素莫匹罗星的抗葡萄球菌、皮肤沉积和皮肤渗透特性。最低抑菌浓度 (MIC) 测定结果表明，TXA497 对高度耐莫匹罗星的 MRSA 仍保持很强的活性。使用 Franz 扩散细胞评估化合物在人体尸体皮肤上的沉积，结果表明 TXA497 的皮肤沉积明显大于莫匹罗星。此外，与莫匹罗星不同，TXA497 不会穿过整个皮肤层，这表明局部给药时该化合物全身吸收的潜力很小。此外，TXA497 的抗菌浓度对原代人角质形成细胞没有明显毒性。鉴于 MRSA 群体中莫匹罗星耐药水平的上升，我们的研究结果意义重大，因为它们突出了 TXA497 作为一种潜在有用的替代疗法，可用于治疗对莫匹罗星耐药的 MRSA 皮肤感染。
