title: Inhalable Antimicrobials for Treatment of Bacterial Biofilm-Associated Sinusitis in Cystic Fibrosis Patients: Challenges and Drug Delivery Approaches.
abstract: Bacterial biofilm-associated chronic sinusitis in cystic fibrosis (CF) patients caused byPseudomonas aeruginosainfections and the lack of available treatments for such infections constitute a critical aspect of CF disease management. Currently, inhalation therapies to combatP. aeruginosainfections in CF patients are focused mainly on the delivery of antimicrobials to the lower respiratory tract, disregarding the sinuses. However, the sinuses constitute a reservoir forP. aeruginosagrowth, leading to re-infection of the lungs, even after clearing an initial lung infection. Eradication ofP. aeruginosafrom the respiratory tract after a first infection has been shown to delay chronic pulmonary infection with the bacteria for up to two years. The challenges with providing a suitable treatment for bacterial sinusitis include: (i) identifying a suitable antimicrobial compound; (ii) selecting a suitable device to deliver the drug to the sinuses and nasal cavities; and (iii) applying a formulation design, which will mediate delivery of a high dose of the antimicrobial directly to the site of infection. This review highlights currently available inhalable antimicrobial formulations for treatment and management of biofilm infections caused byP. aeruginosaand discusses critical issues related to novel antimicrobial drug formulation design approaches.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. sylvia.klodzinska@sund.ku.dk.
authors.forename: Sylvia Natalie
authors.initials: SN
authors.lastname: Kłodzińska
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. psj748@ku.dk.
authors.forename: Petra Alexandra
authors.initials: PA
authors.lastname: Priemel
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. thomas.rades@sund.ku.dk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. hanne.morck@sund.ku.dk.
authors.forename: Hanne
authors.initials: H
authors.lastname: Mørck Nielsen
mesh_terms: D000280:Administration, Inhalation; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D003550:Cystic Fibrosis / Q000150:complications* / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D006801:Humans; D011550:Pseudomonas aeruginosa / Q000502:physiology; D012852:Sinusitis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents; D004337:Drug Carriers
keywords: biofilm; cystic fibrosis; devices; drug delivery; formulation design; inhalable drugs; sinusitis