Enhancing the antibacterial efficacy of low-dose gentamicin with 5 minute assistance of photothermy at 50 °C

Biomater Sci. 2019 Mar 26;7(4):1437-1447. doi: 10.1039/c8bm01539b.

Abstract

Implant materials are prone to bacterial infections and cause serious consequences, while traditional antibiotic therapy has a long treatment cycle and even causes bacterial resistance. In this work, a photothermal therapy (PTT) assisted drug release system has been developed on the implant surface for in situ rapid disinfection under 808 nm light irradiation within a short time, in which gentamicin (Gent) is loaded by polyethylene glycol (PEG) modified molybdenum disulfide (MoS2) on Ti surface, and then encapsulated with chitosan (CS) (CS/Gent/PEG/MoS2-Ti). The hyperthermia produced by the coatings irradiated by 808 nm near-infrared (NIR) light can not only accelerate the local release of Gent, but also reduce the activity of bacteria, which makes it easy for these locally released drugs to enter the interior of the bacteria to inhibit the protein synthesis and destroy the cell membrane. When maintained at 50 °C for 5 min under NIR irradiation, this system can achieve an antibacterial efficacy of 99.93% and 99.19% against Escherichia coli and Staphylococcus aureus, respectively. By contrast, even after treatment for 120 min, only a 93.79% antibacterial ratio can be obtained for Gent alone. This is because hyperthermia produced from the coatings during irradiation can assist antibiotics in killing bacteria in a short time. Even under a low dose of 2 μg mL-1, the photothermal effect assisted gentamicin can achieve an antibacterial efficacy of 96.86% within 5 min. In vitro cell culture shows that the modified surface can facilitate cell adhesion, spreading and proliferation. The 7 day subcutaneous infection model confirms that the prepared surface system can exhibit a much faster sterilization and tissue reconstruction than the control group with light assistance. Compared with the traditional drug release system, this photothermy controlled drug-loaded implant surface system can not only provide rapid and high-efficiency in situ sterilization, but also offer long-term prevention of local bacterial infection.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Disulfides / chemistry
  • Disulfides / pharmacology
  • Escherichia coli / drug effects*
  • Gentamicins / chemical synthesis
  • Gentamicins / chemistry
  • Gentamicins / pharmacology*
  • Male
  • Mice
  • Microbial Sensitivity Tests
  • Molybdenum / chemistry
  • Molybdenum / pharmacology
  • NIH 3T3 Cells
  • Particle Size
  • Phototherapy*
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Staphylococcal Infections / drug therapy
  • Staphylococcus aureus / drug effects*
  • Surface Properties
  • Temperature*
  • Titanium / chemistry
  • Titanium / pharmacology

Substances

  • Anti-Bacterial Agents
  • Disulfides
  • Gentamicins
  • Polyethylene Glycols
  • Molybdenum
  • Titanium
  • molybdenum disulfide