title: Mannitol-guided delivery of Ciprofloxacin in artificial cystic fibrosis mucus model.
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.
authors.affiliation: College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana 47907, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Michael D
authors.initials: MD
authors.lastname: Tsifansky
authors.forename: Sooyoung
authors.initials: S
authors.lastname: Shin
authors.forename: Qingnuo
authors.initials: Q
authors.lastname: Lin
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
mesh_terms: D000280:Administration, Inhalation; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004337:Drug Carriers / Q000378:metabolism*; D006801:Humans; D008353:Mannitol / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012965:Sodium Chloride / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D004337:Drug Carriers; D008353:Mannitol; D012965:Sodium Chloride; D002939:Ciprofloxacin