TY - JOUR
T1 - Developing ciprofloxacin dry powder for inhalation: A story of challenges and rational design in the treatment of cystic fibrosis lung infection
T2 - A story of challenges and rational design in the treatment of cystic fibrosis lung infection
AU - Al-Hajj, Nasser
AU - O'Reilly, Niall
AU - Fox, Helen
N1 - Funding Information:
The research conducted in this publication was funded by the Irish Research Council under award number [GOIPG/2021/26]; Funding from the Waterford Institute of Technology PhD scholarship programme (Nasser Al-hajj) is gratefully acknowledged.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2022/2/5
Y1 - 2022/2/5
N2 - Cystic fibrosis (CF) is an inherited multisystem disease affecting the lung which leads to a progressive decline in lung function as a result of malfunctioning mucociliary clearance and subsequent chronic bacterial infections. Pseudomonas aeruginosa is the predominant cause of lung infection in CF patients and is associated with significant morbidity and mortality. Thus, antibiotic therapy remains the cornerstone of the treatment of CF. Pulmonary delivery of antibiotics for lung infections significantly reduces the required dose and the associated systemic side effects while improving therapeutic outcomes. Ciprofloxacin is one of the most widely used antibiotics against P. aeruginosa and the most effective fluoroquinolone. However, in spite of the substantial amount of research aimed at developing ciprofloxacin powder for inhalation, none of these formulations has been commercialized. Here, we present an integrated view of the diverse challenges associated with delivering ciprofloxacin dry particles to the lungs of CF patients and the rationales behind recent formulations of ciprofloxacin dry powder for inhalation. This review will discuss the challenges in developing ciprofloxacin powder for inhalation along with the physiological and pathophysiological challenges such as ciprofloxacin lung permeability, overproduction of viscous mucus and bacterial biofilms. The review will also discuss the current and emerging particle engineering approaches to overcoming these challenges. By doing so, we believe the review will help the reader to understand the current limitations in developing an inhalable ciprofloxacin powder and explore new opportunities of rational design strategies.
AB - Cystic fibrosis (CF) is an inherited multisystem disease affecting the lung which leads to a progressive decline in lung function as a result of malfunctioning mucociliary clearance and subsequent chronic bacterial infections. Pseudomonas aeruginosa is the predominant cause of lung infection in CF patients and is associated with significant morbidity and mortality. Thus, antibiotic therapy remains the cornerstone of the treatment of CF. Pulmonary delivery of antibiotics for lung infections significantly reduces the required dose and the associated systemic side effects while improving therapeutic outcomes. Ciprofloxacin is one of the most widely used antibiotics against P. aeruginosa and the most effective fluoroquinolone. However, in spite of the substantial amount of research aimed at developing ciprofloxacin powder for inhalation, none of these formulations has been commercialized. Here, we present an integrated view of the diverse challenges associated with delivering ciprofloxacin dry particles to the lungs of CF patients and the rationales behind recent formulations of ciprofloxacin dry powder for inhalation. This review will discuss the challenges in developing ciprofloxacin powder for inhalation along with the physiological and pathophysiological challenges such as ciprofloxacin lung permeability, overproduction of viscous mucus and bacterial biofilms. The review will also discuss the current and emerging particle engineering approaches to overcoming these challenges. By doing so, we believe the review will help the reader to understand the current limitations in developing an inhalable ciprofloxacin powder and explore new opportunities of rational design strategies.
KW - Antibiotics
KW - Ciprofloxacin
KW - Cystic fibrosis
KW - Dry powder inhaler
KW - Pseudomonas aeruginosa
KW - Rational design
UR - http://dx.doi.org/10.1016/j.ijpharm.2021.121388
U2 - 10.1016/j.ijpharm.2021.121388
DO - 10.1016/j.ijpharm.2021.121388
M3 - Review article
C2 - 34923051
AN - SCOPUS:85121484789
VL - 613
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 121388
ER -