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J Pharm Sci. 2014 Apr;103(4):1115-25. doi: 10.1002/jps.23874. Epub 2014 Feb 7.

Steroid-decorated antibiotic microparticles for inhaled anti-infective therapy.

Author information

1
Institute of Chemical and Engineering Sciences, A*STAR (Agency for Science, Technology and Research), Jurong Island, Singapore, 627833, Singapore; Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore.

Abstract

Despite advances in vaccination and antimicrobial therapy, community-acquired pneumonia (CAP) remains as a leading cause of morbidity and mortality worldwide. As the severity of CAP has been linked to the extent of inflammation in the body, adjunctive therapeutic measures aimed at modulating the immune response have therefore become increasingly attractive in recent years. In particular, for CAP patients with underlying medical conditions such as chronic obstructive pulmonary disease (COPD), a steroid-antibiotic combination will no doubt be a useful and timely therapeutic intervention. Unfortunately, no combined steroid-antibiotic dry powder formulation is available commercially or has been reported in the academic literature. The aim of this work was hence to develop a novel steroid-antibiotic dry powder inhaler formulation [ciprofloxacin hydrochloride (CIP) and beclomethasone dipropionate (BP)] for inhaled anti-infective therapy. The spray-dried powder was of respirable size (d50 of ∼2.3 μm), partially crystalline and had BP preferentially deposited on the particle surface. Favorably, when formulated as a binary mix, both CIP and BP showed much higher drug release and fine particle fractions (of the loaded dose) over their singly delivered counterparts, and had robust activity against the respiratory tract infection-causing bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus.

KEYWORDS:

aerosols; antiinfectives; chronic obstructive pulmonary disease (COPD); combinatorial therapy; community-acquired pneumonia (CAP); corticosteroids; dry powder inhaler; formulation; pulmonary drug delivery; spray drying

PMID:
24510431
DOI:
10.1002/jps.23874
[Indexed for MEDLINE]
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