Next Article in Journal
Liposome-Embedding Silicon Microparticle for Oxaliplatin Delivery in Tumor Chemotherapy
Next Article in Special Issue
Itaconic Acid Increases the Efficacy of Tobramycin against Pseudomonas aeruginosa Biofilms
Previous Article in Journal
A Mechanistic, Enantioselective, Physiologically Based Pharmacokinetic Model of Verapamil and Norverapamil, Built and Evaluated for Drug–Drug Interaction Studies
Previous Article in Special Issue
Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria
Open AccessArticle

Comparison between Colistin Sulfate Dry Powder and Solution for Pulmonary Delivery

1
INSERM U1070 “Pharmacology of anti-infective agents”, 1 rue Georges Bonnet, Pôle Biologie Santé, 86022 Poitiers Cedex, France
2
UFR Médecine-Pharmacie Université de Poitiers, 6 rue de la milétrie, TSA 51115, 86073 Poitiers Cedex 9, France
3
Laboratoire de Toxicologie-Pharmacocinétique, CHU de Poitiers, 2 rue de la Miletrie, 86021 Poitiers Cedex, France
4
SSPC, The Science Foundation Ireland Research Centre for Pharmaceuticals, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Panoz Institute, D02 PN40 Dublin 2, Ireland
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(6), 557; https://doi.org/10.3390/pharmaceutics12060557
Received: 8 May 2020 / Revised: 11 June 2020 / Accepted: 13 June 2020 / Published: 17 June 2020
(This article belongs to the Special Issue Drug Delivery for Anti-Infective Agents)
To assess the difference in the fate of the antibiotic colistin (COLI) after its pulmonary delivery as a powder or a solution, we developed a COLI powder and evaluated the COLI pharmacokinetic properties in rats after pulmonary administration of the powder or the solution. The amorphous COLI powder prepared by spray drying was characterized by a mass median aerodynamic diameter and fine particle fraction of 2.68 ± 0.07 µm and 59.5 ± 5.4%, respectively, when emitted from a Handihaler®. After intratracheal administration, the average pulmonary epithelial lining fluid (ELF): plasma area under the concentration versus time curves (AUC) ratios were 570 and 95 for the COLI solution and powder, respectively. However, the same COLI plasma concentration profiles were obtained with the two formulations. According to our pharmacokinetic model, this difference in ELF COLI concentration could be due to faster systemic absorption of COLI after the powder inhalation than for the solution. In addition, the COLI apparent permeability (Papp) across a Calu-3 epithelium model increased 10-fold when its concentration changed from 100 to 4000 mg/L. Based on this last result, we propose that the difference observed in vivo between the COLI solution and powder could be due to a high local ELF COLI concentration being obtained at the site where the dry particles impact the lung. This high local COLI concentration can lead to a local increase in COLI Papp, which is associated with a high concentration gradient and could produce a high local transfer of COLI across the epithelium and a consequent increase in the overall absorption rate of COLI. View Full-Text
Keywords: colistin dry powder inhalation; pulmonary infections; nebulization; pharmacokinetics modeling; Calu-3 permeability colistin dry powder inhalation; pulmonary infections; nebulization; pharmacokinetics modeling; Calu-3 permeability
Show Figures

Figure 1

MDPI and ACS Style

Tewes, F.; Brillault, J.; Gregoire, N.; Olivier, J.-C.; Lamarche, I.; Adier, C.; Healy, A.-M.; Marchand, S. Comparison between Colistin Sulfate Dry Powder and Solution for Pulmonary Delivery. Pharmaceutics 2020, 12, 557. https://doi.org/10.3390/pharmaceutics12060557

AMA Style

Tewes F, Brillault J, Gregoire N, Olivier J-C, Lamarche I, Adier C, Healy A-M, Marchand S. Comparison between Colistin Sulfate Dry Powder and Solution for Pulmonary Delivery. Pharmaceutics. 2020; 12(6):557. https://doi.org/10.3390/pharmaceutics12060557

Chicago/Turabian Style

Tewes, Frédéric; Brillault, Julien; Gregoire, Nicolas; Olivier, Jean-Christophe; Lamarche, Isabelle; Adier, Christophe; Healy, Anne-Marie; Marchand, Sandrine. 2020. "Comparison between Colistin Sulfate Dry Powder and Solution for Pulmonary Delivery" Pharmaceutics 12, no. 6: 557. https://doi.org/10.3390/pharmaceutics12060557

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop