Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA.
Berthiaume Institute for Precision Health, University of Notre Dame, Notre Dame, IN 46556, USA.
Mil Med. 2024 Aug 19;189(Suppl 3):230-238. doi: 10.1093/milmed/usae079.
The purpose of the present study was to create resorbable nanoparticles (NPs) using poly(lactic-co-glycolic acid) (PLGA) to develop novel antibacterial therapeutics for the treatment of chronic wound infections that are susceptible to recurrent infections. By first performing a release study, it was possible to predict the behavior of the different PLGA NP formulations and assess the efficacy of the nanocomposite drug delivery system. These PLGA NP formulations consisted of varying ratios of PLGA without polyvinyl alcohol (PVA) and PLGA with PVA (PLGA-PVA) (i.e., 25:75[PLGA25], 50:50[PLGA50], and 75:25[PLGA75]). Then, different antibiotics (i.e., ciprofloxacin and gentamicin) were incorporated into the PLGA NP formulations to test the antibacterial efficacy of these antimicrobial NPs against different pathogens (i.e., methicillin-resistant Staphylococcus aureus USA300 [MRSA], Pseudomonas aeruginosa FRD1, and Acinetobacter baumannii BAA1605). Of particular interest was testing against the MRSA strain USA300 and the P. aeruginosa strain FRD1. This was possible by measuring the zone of inhibition. A 3-day period was used to monitor the antibacterial efficacy of the different PLGA NP formulations (i.e., PLGA25, PLGA50, and a 1:1 combination of PLGA25:PLGA50) against A. baumannii BAA1605, MRSA, and P aeruginosa FRD1. Throughout the study, A. baumannii was a negative control and was resistant to all the PLGA NP formulations loaded with ciprofloxacin and gentamicin. At the end of the 3-day period, the PLGA and PLGA50 ciprofloxacin-loaded formulations produced zones of inhibition of 27 mm and 23 mm, respectively, against P. aeruginosa FRD1. This indicated that P. aeruginosa FRD1 was susceptible to both formulations. The mixed formulations with equal parts PLGA25:PLGA50 loaded with ciprofloxacin produced a zone of inhibition (i.e., 25 mm). This again indicated that P. aeruginosa FRD1 was susceptible to ciprofloxacin. The formulations tested against MRSA showed that only gentamicin-loaded formulations produced intermediate results, and that ciprofloxacin-loaded formulations were ineffective. The PLGA25 and the PLGA50 NP formulations loaded with gentamicin both produced zones of inhibition of 13 mm. This indicated that MRSA was intermediate to both the formulations. The PLGA25:PLGA50 loaded with gentamicin produced a zone of inhibition of 14 mm, which again showed that MRSA was intermediate to this formulation. Overall, these PLGA NP formulations showed the sustained antibacterial potential of a burst release, followed by a sustained release of antibiotics from antibiotics loaded PLGA NPs in a controlled manner. In the future, this can help prevent the emergence of recurrent infections in the treatment of chronic wounds and reduce the number of medical dressing changes.
本研究的目的是使用聚（乳酸-共-乙醇酸）（PLGA）制备可吸收纳米颗粒（NPs），以开发用于治疗易发生复发性感染的慢性伤口感染的新型抗菌疗法。通过首先进行释放研究，可以预测不同 PLGA NP 制剂的行为，并评估纳米复合材料药物递送系统的疗效。这些 PLGA NP 制剂由不同比例的不含聚乙烯醇（PVA）的 PLGA 和含 PVA 的 PLGA（PLGA-PVA）组成（即 25:75[PLGA25]、50:50[PLGA50]和 75:25[PLGA75]）。然后，将不同的抗生素（即环丙沙星和庆大霉素）掺入 PLGA NP 制剂中，以测试这些抗菌 NPs 对不同病原体（即耐甲氧西林金黄色葡萄球菌美国 300 型[MRSA]、铜绿假单胞菌 FRD1 和鲍曼不动杆菌 BAA1605）的抗菌功效。特别感兴趣的是测试对 MRSA 菌株 USA300 和铜绿假单胞菌 FRD1 的抑制作用。通过测量抑菌圈，可以实现这一点。使用 3 天的时间来监测不同 PLGA NP 制剂（即 PLGA25、PLGA50 和 PLGA25：PLGA50 的 1:1 组合）对鲍曼不动杆菌 BAA1605、MRSA 和铜绿假单胞菌 FRD1 的抗菌功效。在整个研究过程中，鲍曼不动杆菌是阴性对照，对载有环丙沙星和庆大霉素的所有 PLGA NP 制剂均具有抗性。在 3 天的研究结束时，载有环丙沙星的 PLGA 和 PLGA50 制剂分别对铜绿假单胞菌 FRD1 产生了 27mm 和 23mm 的抑菌圈。这表明铜绿假单胞菌 FRD1 对这两种制剂均敏感。载有等量 PLGA25：PLGA50 的混合制剂载有环丙沙星，产生了 25mm 的抑菌圈。这再次表明铜绿假单胞菌 FRD1 对环丙沙星敏感。针对 MRSA 的制剂测试表明，只有载有庆大霉素的制剂产生了中等结果，而载有环丙沙星的制剂无效。载有庆大霉素的 PLGA25 和 PLGA50 NP 制剂均产生了 13mm 的抑菌圈。这表明 MRSA 对这两种制剂均呈中介。载有庆大霉素的 PLGA25：PLGA50 产生了 14mm 的抑菌圈，这再次表明该制剂对 MRSA 呈中介。总体而言，这些 PLGA NP 制剂表现出了抗生素负载的 PLGA NPs 以控制方式持续释放抗生素的爆发式和持续释放的持续抗菌潜力。将来，这有助于预防慢性伤口治疗中复发性感染的出现，并减少医疗敷料更换的次数。
