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

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:

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

Acknowledgments

The authors thank Margrit Leitner, University Hospital Jena, Centre for Sepsis Control and Care, for proofreading the manuscript. M Klinger-Strobel and C Lautenschläger have equally contributed to this manuscript.

Declaration of interest

This work was supported by grants from the German Ministry of Education and Research (BMBF), grant numbers 01KI1204 and 01EO1002, as well as by the Deutsche Forschungsgemeinschaft, DFG, grant PL 320/3-1 and FI 899/4-1. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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