Aspects of pulmonary drug delivery strategies for infections in cystic fibrosis--where do we stand?

Expert Opin Drug Deliv. 2015 Aug;12(8):1351-74. doi: 10.1517/17425247.2015.1007949. Epub 2015 Feb 2.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords: Burkholderia cepacia complex; Pseudomonas aeruginosa; Staphylococcus aureus; amikacin; aztreonam lysine; biofilms; colistin; nanoparticles; poly(lactic-co-glycolic acid); tobramycin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Inhalation
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Cystic Fibrosis / drug therapy*
  • Drug Delivery Systems*
  • Humans
  • Lung / microbiology
  • Lung / physiopathology
  • Pseudomonas Infections / drug therapy
  • Pseudomonas aeruginosa / drug effects

Substances

  • Anti-Bacterial Agents