title: Drug and light delivery strategies for photodynamic antimicrobial chemotherapy (PACT) of pulmonary pathogens: a pilot study.
abstract: Pulmonary disease is the main cause of morbidity and mortality in cystic fibrosis (CF) suffers, with multidrug-resistant Pseudomonas aeruginosa and Burkholderia cepacia complex as problematic pathogens in terms of recurrent and unremitting infections. Novel treatment of pulmonary infection is required to improve the prognosis and quality of life for chronically infected patients. Photodynamic antimicrobial chemotherapy (PACT) is a treatment combining exposure to a light reactive drug, with light of a wavelength specific for activation of the drug, in order to induce cell death of bacteria. Previous studies have demonstrated the susceptibility of CF pathogens to PACT in vitro. However, for the treatment to be of clinical use, light and photosensitizer must be able to be delivered successfully to the target tissue. This preliminary study assessed the potential for delivery of 635 nm light and methylene blue to the lung using an ex vivo and in vitro lung model. Using a fibre-optic light delivery device coupled to a helium-neon laser, up to 11% of the total light dose penetrated through full thickness pulmonary parenchymal tissue, which indicates potential for multiple lobe irradiation in vivo. The mass median aerodynamic diameter (MMAD) of particles generated via methylene blue solution nebulisation was 4.40 μm, which is suitable for targeting the site of infection within the CF lung. The results of this study demonstrate the ability of light and methylene blue to be delivered to the site of infection in the CF lung. PACT remains a viable option for selective killing of CF lung pathogens.
authors.affiliation: School of Pharmacy, Queens University Belfast, Medical Biology Centre, Belfast, UK.
authors.forename: Corona M
authors.initials: CM
authors.lastname: Cassidy
authors.forename: Michael M
authors.initials: MM
authors.lastname: Tunney
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Magee
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Elborn
authors.forename: Steven
authors.initials: S
authors.lastname: Bell
authors.forename: Thakur Raghu Raj
authors.initials: TR
authors.lastname: Singh
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy*; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004339:Drug Compounding / Q000379:methods; D066298:In Vitro Techniques; D008168:Lung / Q000382:microbiology / Q000502:physiology / Q000528:radiation effects*; D008751:Methylene Blue / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011836:Radiation Tolerance / Q000502:physiology; D012542:Scattering, Radiation; D013552:Swine; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D000890:Anti-Infective Agents; D017319:Photosensitizing Agents; D008751:Methylene Blue