title: Aspects of pulmonary drug delivery strategies for infections in cystic fibrosis--where do we stand?
abstract: BACKGROUND
  Cystic fibrosis (CF) is the most common life-shortening hereditary disease among Caucasians and is associated with severe pulmonary damage because of decreased mucociliary clearance and subsequent chronic bacterial infections. Approximately 90% of CF patients die from lung destruction, promoted by pathogens such as Pseudomonas aeruginosa. Consequently, antibiotic treatment is a cornerstone of CF therapy, preventing chronic infection and reducing bacterial load, exacerbation rates and loss of pulmonary function. Many drugs are administered by inhalation to achieve high pulmonary concentration and to lower systemic side effects. However, pulmonary deposition of inhaled drugs is substantially limited by bronchial obstruction with viscous mucus and restrained by intrapulmonary bacterial biofilms.
  
  
  METHODS
  This review describes challenges in the therapy of CF-associated infections by inhaled antibiotics and summarizes the current state of microtechnology and nanotechnology-based pulmonary antibiotic delivery strategies. Recent and ongoing clinical trials as well as experimental approaches for microparticle/nanoparticle-based antibiotics are presented and their advantages and disadvantages are discussed.
  
  
  CONCLUSIONS
  Rapidly increasing antimicrobial resistance accompanied by the lack of novel antibiotics force targeted and more efficient use of the available drugs. Encapsulation of antimicrobials in nanoparticles or microparticles of organic polymers may have great potential for use in CF therapy.
authors: Jena University Hospital, Center for Infectious Diseases and Infection Control , Erlanger Allee 101, 07740 Jena , Germany +49 3641 9324227 ; oliwia.makarewicz@med.uni-jena.de.
authors: Mareike
authors: M
authors: Klinger-Strobel
authors: Christian
authors: C
authors: Lautenschläger
authors: Dagmar
authors: D
authors: Fischer
authors: Jochen G
authors: JG
authors: Mainz
authors: Tony
authors: T
authors: Bruns
authors: Lorena
authors: L
authors: Tuchscherr
authors: Mathias W
authors: MW
authors: Pletz
authors: Oliwia
authors: O
authors: Makarewicz
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D003550:Cystic Fibrosis / Q000188:drug therapy*; D016503:Drug Delivery Systems; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000503:physiopathology; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents
keywords: Burkholderia cepacia complex; Pseudomonas aeruginosa; Staphylococcus aureus; amikacin; aztreonam lysine; biofilms; colistin; nanoparticles; poly(lactic-co-glycolic acid); tobramycin