Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, U.P., 221005, India.
Department of Microbiology, Institute of Medical Science, Banaras Hindu University, Varanasi, U.P., 221005, India.
AAPS PharmSciTech. 2023 Aug 8;24(6):165. doi: 10.1208/s12249-023-02620-w.
Klebsiella pneumoniae is regarded as one of the most profound bacteria isolated from the debilitating injuries caused by burn wounds. In addition, the multidrug resistance (MDR) and biofilm formation make treating burn patients with clinically available antibiotics difficult. Bacteriophage therapy has been proven an effective alternative against biofilm-mediated wound infections caused by MDR bacterial strains. In the current study, the bacteriophage (BPKPФ1) against MDR Klebsiella pneumoniae was isolated and loaded into the chitosan microparticles (CHMPs), which was later incorporated into the Sepineo P 600 to convert into a gel (BPKPФ1-CHMP-gel). BPKPФ1 was characterized for lytic profile, morphological class, and burst size, which revealed that the BPKPФ1 belongs to the family Siphoviridae. Moreover, BPKPФ1 exhibited a narrow host range with 128 PFU/host cell of burst size. The BPKPФ1-loaded CHMPs showed an average particle size of 1.96 ± 0.51 μm, zeta potential 32.16 ± 0.41 mV, and entrapment efficiency in the range of 82.44 ± 1.31%. Further, the in vitro antibacterial and antibiofilm effectiveness of BPKPФ1-CHMPs-gel were examined. The in vivo potential of the BPKPФ1-CHMPs-gel was assessed using a rat model with MDR Klebsiella pneumoniae infected burn wound, which exhibited improved wound contraction (89.22 ± 0.48%) in 28 days with reduced inflammation, in comparison with different controls. Data in hand suggest the potential of bacteriophage therapy to be developed as personalized therapy in case of difficult-to-treat bacterial infections.
肺炎克雷伯菌被认为是从烧伤伤口引起的衰弱性损伤中分离出来的最严重的细菌之一。此外,多药耐药(MDR)和生物膜形成使得用临床可用的抗生素治疗烧伤患者变得困难。噬菌体治疗已被证明是对抗由 MDR 细菌引起的生物膜介导的伤口感染的有效替代方法。在目前的研究中,分离出针对 MDR 肺炎克雷伯菌的噬菌体(BPKPФ1)并将其装载到壳聚糖微球(CHMPs)中,然后将其掺入 Sepineo P 600 中转化为凝胶(BPKPФ1-CHMP-gel)。对 BPKPФ1 的裂解谱、形态分类和爆发大小进行了表征,结果表明 BPKPФ1 属于肌尾噬菌体科。此外,BPKPФ1 表现出狭窄的宿主范围,爆发大小为 128 PFU/宿主细胞。载有 BPKPФ1 的 CHMPs 的平均粒径为 1.96 ± 0.51 μm,Zeta 电位为 32.16 ± 0.41 mV,包封效率在 82.44 ± 1.31%范围内。进一步研究了 BPKPФ1-CHMPs-gel 的体外抗菌和抗生物膜效果。使用 MDR 肺炎克雷伯菌感染烧伤创面的大鼠模型评估了 BPKPФ1-CHMPs-gel 的体内潜力,结果显示在 28 天内,与不同对照相比,伤口收缩率提高(89.22 ± 0.48%),炎症减轻。目前的数据表明,噬菌体治疗具有开发为针对难以治疗的细菌感染的个体化治疗的潜力。