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Mannitol-Guided delivery of ciprofloxacin in artificial cystic fibrosis mucus model

Authors

  • Yan Yang,

    1. College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907; telephone: +1-765-496-9608; fax: +1-765-494-6545
    2. Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun, PR China
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  • Michael D. Tsifansky,

    1. Department of Pediatrics, Divisions of Pediatric Critical Care Medicine and Pediatric Pulmonology, Advocate Lutheran General Children's Hospital, Park Ridge, Illinois
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  • Sooyoung Shin,

    1. College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907; telephone: +1-765-496-9608; fax: +1-765-494-6545
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  • Qingnuo Lin,

    1. College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907; telephone: +1-765-496-9608; fax: +1-765-494-6545
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  • Yoon Yeo

    Corresponding author
    1. College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907; telephone: +1-765-496-9608; fax: +1-765-494-6545
    2. Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana
    • College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907; telephone: +1-765-496-9608; fax: +1-765-494-6545.
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Abstract

Abnormal airway mucus presents a significant challenge for inhalational drug delivery. Recognizing the thick and tenacious airway mucus seen in the cystic fibrosis (CF) patients as a critical barrier to effective drug delivery, both into the mucus layer itself as well as across that layer to the underlying airway epithelium, we hypothesize that mannitol or NaCl can form inhalable drug carriers, improve drug penetration into the mucus, and ultimately enhance the drug's therapeutic effect. The objective of this study is to test whether mannitol and NaCl particles, as inhalable drug carriers, improve drug delivery into and enhance a drug's activity within a mucus-like material. Microparticles containing Ciprofloxacin (Cipro), an active ingredient, and either mannitol or NaCl were produced by spray-drying. Cipro encapsulated in mannitol particles (Cipro–mannitol) was significantly more effective at killing Pseudomonas aeruginosa (P. aeruginosa) grown in artificial mucus (AM) than Cipro encapsulated in either NaCl particles (Cipro–NaCl) or in hydrophobic particles consisting of dipalmitoylphosphatidylcholine (DPPC), albumin, and lactose (Cipro–DAL). The relatively high antibacterial effectiveness of Cipro–mannitol was not due to the effect of mannitol on bacteria or on Cipro. Rather, the unique performance of the mannitol-based particles in AM is attributable to its ability to increase local water content in the AM and enhance drug penetration into it. Mannitol is a promising excipient for inhalable microparticles that facilitate the drug delivery into the CF mucus. Biotechnol. Bioeng. 2011; 108:1441–1449. © 2010 Wiley Periodicals, Inc.

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