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Topical application of bacteriophages for treatment of wound infections.

ABSTRACT: Wound infections associated with multidrug-resistant (MDR) bacteria are one of the important threats to public health. Bacteriophage (phage) therapy is a promising alternative or supplementary therapeutic approach to conventional antibiotics for combating MDR bacterial infections. In recent years, significant effort has been put into the development of phage formulations and delivery methods for topical applications, along with preclinical and clinical uses of phages for the treatment of acute and chronic wound infections. This paper reviews the application of phages for wound infections, with focus on the current status of phage formulations (including liquid, semi-solid and liposome-encapsulated formulations, phage-immobilized wound dressings), safety and efficacy assessment in clinical settings and major challenges to overcome.

SUBMITTER: Chang RYK

PROVIDER: S-EPMC7293950 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Topical application of bacteriophages for treatment of wound infections.

Chang Rachel Yoon Kyung RYK Morales Sandra S Okamoto Yuko Y Chan Hak-Kim HK

Translational research : the journal of laboratory and clinical medicine 20200319

Wound infections associated with multidrug-resistant (MDR) bacteria are one of the important threats to public health. Bacteriophage (phage) therapy is a promising alternative or supplementary therapeutic approach to conventional antibiotics for combating MDR bacterial infections. In recent years, significant effort has been put into the development of phage formulations and delivery methods for topical applications, along with preclinical and clinical uses of phages for the treatment of acute a ...[more]

PMID: 32268129

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Project description:Linezolid (LZ) loaded chitosan-nanoparticles (CSNPs) was developed by the ionic-gelation method using Tripolyphosphate-sodium as a crosslinker for topical application for the treatment of bacterial eye infections. Particles were characterized by Zeta-Sizer (Malvern Nano-series). TEM was used for structural morphology. Encapsulation and drug loading were estimated by measuring the unencapsulated drug. In-vitro drug release in STF (pH 7) was performed through a dialysis membrane. Storage stability of LZ-CSNPs was checked at 25 °C and 40 °C for six months. The antimicrobial potency of NPs was evaluated on different Gram-positive strains. Ocular irritation and pharmacokinetic studies were completed in rabbits. Ex-vivo transcorneal permeation of the drug was determined through the rabbit cornea. Ionic interaction among the oppositely charged functional groups of CS and TPP generated the CSNPs. The weight ratio at 3:1, wt/wt (CS/TPP) with 21.7 mg of LZ produced optimal NPs (213.7 nm with 0.387 of PDI and +23.1 mV of ZP) with 71% and 11.2% encapsulation and drug loading, respectively. Around 76.7% of LZ was released from LZ-AqS within 1 h, while 79.8% of LZ was released from CSNPs at 12 h and 90% at 24 h. The sustained drug release property of CSNPS was evaluated by applying kinetic models. The linearity in the release profile suggested that the release of LZ from CSNPs followed the Higuchi-Matrix model. LZ-CSNPs have shown 1.4 to 1.6-times improved antibacterial activity against the used bacterial strains. The LZ-CSNPs were "minimally-irritating" to rabbit eyes and exhibited 4.4-times increased transcorneal permeation of LZ than from LZ-AqS. Around 3-, 1.2- and 3.1-times improved Tmax, Cmax, and AUC0-24 h, respectively were found for LZ-CSNPs during the ocular pharmacokinetic study. AqS has shown 3.1-times faster clearance of LZ. Conclusively, LZ-CSNPs could offer a better alternative for the prolonged delivery of LZ for the treatment of bacterial infections in the eyes.

Project description:Multi-drug resistance has become a major problem for the treatment of pathogenic bacterial infections. The use of bacteriophages is an attractive approach to overcome the problem of drug resistance in several pathogens that cause fatal diseases. Our study aimed to isolate multi drug resistant bacteria from patients with septic wounds and then isolate and apply bacteriophages in vitro as alternative therapeutic agents. Pus samples were aseptically collected from Rajiv Gandhi Institute of Medical Science (RIMS), Kadapa, A.P., and samples were analyzed by gram staining, evaluating morphological characteristics, and biochemical methods. MDR-bacterial strains were collected using the Kirby-Bauer disk diffusion method against a variety of antibiotics. Bacteriophages were collected and tested in vitro for lytic activity against MDR-bacterial isolates. Analysis of the pus swab samples revealed that the most of the isolates detected had Pseudomonas aeruginosa as the predominant bacterium, followed by Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli. Our results suggested that gram-negative bacteria were more predominant than gram-positive bacteria in septic wounds; most of these isolates were resistant to ampicillin, amoxicillin, penicillin, vancomycin and tetracycline. All the gram-positive isolates (100%) were multi-drug resistant, whereas 86% of the gram-negative isolates had a drug resistant nature. Further bacteriophages isolated from sewage demonstrated perfect lytic activity against the multi-drug resistant bacteria causing septic wounds. In vitro analysis of the isolated bacteriophages demonstrated perfect lysis against the corresponding MDR-bacteria, and these isolated phages may be promising as a first choice for prophylaxis against wound sepsis, Moreover, phage therapy does not enhance multi-drug resistance in bacteria and could work simultaneously on a wide variety of MDR-bacteria when used in a bacteriophage cocktail. Hence, our results suggest that these bacteriophages could be potential therapeutic options for treating septic wounds caused by P. aeruginosa, S. aureus, K. pneumoniae and E. coli.

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Topical application of bacteriophages for treatment of wound infections.

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Topical application of bacteriophages for treatment of wound infections.

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