Fibrin glue as a local drug-delivery system for bacteriophage PA5

Abstract

Fibrin glue has been used clinically for decades in a wide variety of surgical specialties and is now being investigated as a medium for local, prolonged drug delivery. Effective local delivery of antibacterial substances is important perioperatively in patients with implanted medical devices or postoperatively for deep wounds. However, prolonged local application of antibiotics is often not possible or simply inadequate. Biofilm formation and antibiotic resistance are also major obstacles to antibacterial therapy. In this paper we test the biocompatibility of bacteriophages incorporated within fibrin glue, track the release of bacteriophages from fibrin scaffolds, and measure the antibacterial activity of released bacteriophages. Fibrin glue polymerized in the presence of the PA5 bacteriophage released high titers of bacteriophages during 11 days of incubation in liquid medium. Released PA5 bacteriophages were effective in killing Pseudomonas aeruginosa PA01. Overall, our results show that fibrin glue can be used for sustained delivery of bacteriophages and this strategy holds promise for many antibacterial applications.

The Adenosine A2A Receptor Agonist Accelerates Bone Healing and Adjusts Treg/Th17 Cell Balance through Interleukin 6

“…System. The preparation of the fibrin glue and the selection of the A2A receptor agonist and antagonist doses were based on the methods reported by several articles [27][28][29][30]. Briefly, fibrinogen powder (Solarbio, China) was dissolved in physiological saline into a concentration with 10 mg/ml at 37°C.…”

Local Bacteriophage Delivery for Treatment and Prevention of Bacterial Infections

“…Recently, Rubalskii et al (2019) used a commercially available fibrin glue (TISSEEL ® ) to embed bacteriophages and use this fibrin glue for Pseudomonas aeruginosa phage PA01 delivery to treat local infections. The fibrin matrix was completely dissolved after 11 days of incubation in saline solution but throughout this period, phages were consistently released at high titers of approximately 10 9 PFU/mL.…”

Commentary: Leveraging operative exposure—Future “targeted” opportunity or disappointment?

“…3 In addition, they can be filled with other specific chemotherapeutic nanoparticles, or even virus payloads that target biofilm-producing bacteria to reduce infections. 4,5 Even as we embrace minimally invasive surgery, our colleagues similarly have been developing competitive, less toxic, and more targeted chemotherapy and radiation, which we offer to our patients as their general thoracic oncology disease managers. During our operative exposure, we routinely control ventilation, pulmonary blood flow, and pleural drainage selectively.…”