Nitric oxide releasing poly(vinylidene fluoride-co-hexafluoropropylene) films using a fluorinated nitric oxide donor to greatly decrease chemical leaching

Abstract

Nitric oxide (NO) releasing polymers have been widely applied as biomaterials for a variety of biomedical implants and devices. However, the chemical leaching of NO donors and their byproduct species is almost always observed during the application of polymers doped with NO donors, unless the donor is covalently linked to the polymer. Herein, we report the first NO releasing poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) fluorinated copolymer prepared by incorporating a fluorinated S-nitrosothiol as the NO donor. Under physiological conditions, the resulting polymeric films can release NO for 16 days. Importantly, due to both fluorine-fluorine and electrostatic charge interactions between the fluorinated NO donor and the PVDF-HFP copolymer, the total chemical leaching of the fluorinated NO donor and its disulfide product after 9 day was only 0.6% (mol%) of the initial amount of NO donor loaded into the film. These new NO release PVDF-HFP films exhibit antimicrobial and anti-biofilm activities against both Gram positive S. aureus and Gram negative P. aeruginosa strains. The NO-releasing PVDF-HFP polymer can also be coated on Teflon tubing to release NO under physiological conditions for extended time periods. This NO-releasing PVDF-HFP copolymer with greatly reduced chemical leaching could help enhance the biocompatibility and antimicrobial activity of various biomedical devices.

Versatile polymer-based strategies for antibacterial drug delivery systems and antibacterial coatings

“…50 Gaseous NO molecules are difficult to deliver in the body. NO donors, such as S-nitrosothiols (RSNOs), 11,51 N-diazeniumdiolates (NONOates) 52 and other donors are mainly used to deliver NO to the infected site. However, most of the NO donors are unstable and easily decompose to produce by-products such as disulfides.…”

Nitric Oxide-Releasing Polymeric Materials for Antimicrobial Applications: A Review

“…Fluorinated polymers such as polytetrafluoroethylene (PTFE) and polyvinylidene fluoride (PVDF) are widely used to prepare various biomedical implants and devices because of their excellent mechanical properties, great thermal stability, high chemical inertness, and improved biocompatibility [165,166]. Owing to the highly hydrophobic surface property, fluorinated polymers show inherent anti-inflammatory and thromboresistant properties [167]. However, these properties are limited, and further biomedical applications need enhanced antibacterial and antithrombotic properties.…”

“…However, these properties are limited, and further biomedical applications need enhanced antibacterial and antithrombotic properties. Doping NO donors into these fluorinated polymers seems to be a good solution, but poor compatibility between them usually results in a significant amount of chemical leaching [167]. Meyerhoff et al synthesized a fluorinated SNAP derivative C 2 F 5 -SNAP as NO donor and PDVF tubing was swollen in this C 2 F 5 -SNAP solution to prepare C 2 F 5 -SNAP doped PDVF tubing [168].…”

NO donors and NO delivery methods for controlling biofilms in chronic lung infections

“…Fluorinated derivatives of NO donor SNAP, C 2 F 5 -SNAP, and DiCF 3 Bn-SNAP, were doped into polyvinylidene fluoride (PVDF) tubes. These tubes showed significant antimicrobial and antibiofilm activities against S. aureus and P. aeruginosa (Zhou et al 2019 ; Zhou et al 2018 ), suggesting a great potential in the development of antibacterial biomedical devices applied in respiratory diseases.…”