NanoBio Corporation, 2311 Green Rd., Suite A, Ann Arbor, MI 48105, USA.
Antimicrob Agents Chemother. 2011 Sep;55(9):4211-7. doi: 10.1128/AAC.00561-11. Epub 2011 Jul 11.
NB-003 and NB-003 gel formulations are oil-in-water nanoemulsions designed for use in bacterial infections. In vitro susceptibility of Propionibacterium acnes to NB-003 formulations and comparator drugs was evaluated. Both NB-003 formulations were bactericidal against all P. acnes isolates, including those that were erythromycin, clindamycin, and/or tetracycline resistant. In the absence of sebum, the MIC(90)s/minimum bactericidal concentrations (MBC(90)s) for NB-003, NB-003 gel, salicylic acid (SA), and benzoyl peroxide (BPO) were 0.5/2.0, 1.0/2.0, 1,000/2,000, and 50/200 μg/ml, respectively. In the presence of 50% sebum, the MIC(90)s/MBC(90)s of NB003 and BPOs increased to 128/1,024 and 400/1,600 μg/ml, respectively. The MIC(90)s/MBC(90)s of SA were not significantly impacted by the presence of sebum. A reduction in the MBC(90)s for NB-003 and BPO was observed when 2% SA or 0.5% BPO was integrated into the formulation, resulting in MIC(90)s/MBC(90)s of 128/256 μg/ml for NB003 and 214/428 μg/ml for BPO. The addition of EDTA enhanced the in vitro efficacy of 0.5% NB-003 in the presence or absence of 25% sebum. The addition of 5 mM EDTA to each well of the microtiter plate resulted in a >16- and >256-fold decrease in MIC(90) and MBC(90), yielding a more potent MIC(90)/MBC(90) of ≤1/<1 μg/ml. The kinetics of bactericidal activity of NB-003 against P. acnes were compared to those of a commercially available product of BPO. Electron micrographs of P. acnes treated with NB-003 showed complete disruption of bacteria. Assessment of spontaneous resistance of P. acnes revealed no stably resistant mutant strains.
NB-003 和 NB-003 凝胶制剂是设计用于治疗细菌感染的油包水型纳米乳剂。评估了痤疮丙酸杆菌对 NB-003 制剂和比较药物的体外药敏性。两种 NB-003 制剂均对所有痤疮丙酸杆菌分离株具有杀菌作用，包括红霉素、克林霉素和/或四环素耐药株。在没有皮脂的情况下，NB-003、NB-003 凝胶、水杨酸（SA）和过氧化苯甲酰（BPO）的 MIC90/最小杀菌浓度（MBC90）分别为 0.5/2.0、1.0/2.0、1000/2000 和 50/200μg/ml。在存在 50%皮脂的情况下，NB003 和 BPO 的 MIC90/MBC90 分别增加至 128/1024 和 400/1600μg/ml。皮脂的存在并未显著影响 SA 的 MIC90/MBC90。当将 2%SA 或 0.5%BPO 整合到制剂中时，NB-003 和 BPO 的 MBC90 降低，导致 NB003 的 MIC90/MBC90 为 128/256μg/ml，BPO 的 MIC90/MBC90 为 214/428μg/ml。在存在或不存在 25%皮脂的情况下，EDTA 的加入增强了 0.5%NB-003 的体外疗效。在微量滴定板的每个孔中加入 5mM EDTA 可导致 MIC90 和 MBC90 降低>16 倍和>256 倍，产生更有效的 MIC90/MBC90，≤1/<1μg/ml。NB-003 对痤疮丙酸杆菌的杀菌活性动力学与市售 BPO 产品进行了比较。NB-003 处理后的痤疮丙酸杆菌的电子显微镜照片显示细菌完全破裂。对痤疮丙酸杆菌自发耐药性的评估未发现稳定的耐药突变株。
