{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:37:52Z","timestamp":1791333472220,"version":"4.3.1"},"reference-count":110,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T00:00:00Z","timestamp":1683936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"publisher","award":["APP1157287"],"award-info":[{"award-number":["APP1157287"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cystic Fibrosis Australia","award":["APP1157287"],"award-info":[{"award-number":["APP1157287"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Pulmonary drug delivery has long been used for local and systemic administration of different medications used in acute and chronic respiratory diseases. Certain lung diseases, such as cystic fibrosis, rely heavily on chronic treatments, including targeted lung delivery. Pulmonary drug delivery possesses various physiological advantages compared to other delivery methods and is also convenient for the patient to use. However, the formulation of dry powder for pulmonary delivery proves challenging due to aerodynamic restrictions and the lower tolerance of the lung. The aim of this review is to provide an overview of the respiratory tract structure in patients with cystic fibrosis, including during acute and chronic lung infections and exacerbations. Furthermore, this review discusses the advantages of targeted lung delivery, including the physicochemical properties of dry powder and factors affecting clinical efficacy. Current inhalable drug treatments and drugs currently under development will also be discussed.<\/jats:p>","DOI":"10.3390\/pharmaceutics15051488","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T08:28:16Z","timestamp":1684139296000},"page":"1488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Dry Powder Inhalation for Lung Delivery in Cystic Fibrosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Xiaoxuan","family":"Han","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2102-7432","authenticated-orcid":false,"given":"Felisa","family":"Reyes-Ortega","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6044-4824","authenticated-orcid":false,"given":"Elena K.","family":"Schneider-Futschik","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5852","DOI":"10.3390\/ijms15045852","article-title":"Nanoparticle-mediated pulmonary drug delivery: A review","volume":"15","author":"Paranjpe","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrmicro.2017.14","article-title":"The microbiota of the respiratory tract: Gatekeeper to respiratory health","volume":"15","author":"Man","year":"2017","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_3","first-page":"999","article-title":"Morphometry of the human lung: The state of the art after two decades","volume":"15","author":"Weibel","year":"1979","journal-title":"Bull. Eur. Physiopathol. Respir."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chaurasiya, B., and Zhao, Y.Y. (2020). Dry Powder for Pulmonary Delivery: A Comprehensive Review. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010031"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.addr.2007.02.002","article-title":"Application of supercritical fluid to preparation of powders of high-molecular weight drugs for inhalation","volume":"60","author":"Okamoto","year":"2008","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.tibtech.2007.09.005","article-title":"Nanoparticles for drug delivery to the lungs","volume":"25","author":"Sung","year":"2007","journal-title":"Trends Biotechnol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1089\/jamp.2010.0855","article-title":"Development of an inhaled dry-powder formulation of tobramycin using PulmoSphere technology","volume":"24","author":"Geller","year":"2011","journal-title":"J. Aerosol Med. Pulm. Drug. Deliv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"121457","DOI":"10.1016\/j.ijpharm.2022.121457","article-title":"The future of dry powder inhaled therapy: Promising or discouraging for systemic disorders?","volume":"614","author":"Ye","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15010","DOI":"10.1038\/nrdp.2015.10","article-title":"Cystic fibrosis","volume":"1","author":"Ratjen","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Keown, K., Brown, R., Doherty, D.F., Houston, C., McKelvey, M.C., Creane, S., Linden, D., McAuley, D.F., Kidney, J.C., and Weldon, S. (2020). Airway Inflammation and Host Responses in the Era of CFTR Modulators. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176379"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jcf.2015.03.003","article-title":"Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy","volume":"14","author":"Cantin","year":"2015","journal-title":"J. Cyst. Fibros."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.addr.2021.02.017","article-title":"Dry powder pharmaceutical biologics for inhalation therapy","volume":"172","author":"Chang","year":"2021","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.2147\/COPD.S72762","article-title":"Ease-of-use preference for the ELLIPTA(R) dry powder inhaler over a commonly used single-dose capsule dry powder inhaler by inhalation device-naive Japanese volunteers aged 40 years or older","volume":"9","author":"Komase","year":"2014","journal-title":"Int. J. Chron. Obstr. Pulm. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1208\/s12249-015-0317-x","article-title":"Devices for dry powder drug delivery to the lung","volume":"16","author":"Berkenfeld","year":"2015","journal-title":"AAPS PharmSciTech"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1055\/s-0034-1365321","article-title":"Trockenpulverinhalation bei Mukoviszidose","volume":"68","author":"Steinkamp","year":"2014","journal-title":"Pneumologie"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jpba.2017.09.019","article-title":"Physicochemical stability and aerosolization performance of dry powder inhalation system containing ciprofloxacin hydrochloride","volume":"148","author":"Karimi","year":"2018","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v19.i45.40","article-title":"Pulmonary drug delivery systems: Recent developments and prospects","volume":"19","author":"Courrier","year":"2002","journal-title":"Crit. Rev. Ther. Drug. Carr. Syst."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2008.04.044","article-title":"Dry powder inhalers (DPIs)--a review of device reliability and innovation","volume":"360","author":"Islam","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1089\/089426802760292672","article-title":"The role of particle properties in pharmaceutical powder inhalation formulations","volume":"15","author":"Chew","year":"2002","journal-title":"J. Aerosol Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1208\/s12249-009-9313-3","article-title":"Effect of particle shape on dry particle inhalation: Study of flowability, aerosolization, and deposition properties","volume":"10","author":"Hassan","year":"2009","journal-title":"AAPS PharmSciTech"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0378-5173(00)00347-1","article-title":"The influence of carrier morphology on drug delivery by dry powder inhalers","volume":"200","author":"Zeng","year":"2000","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.ajps.2014.12.006","article-title":"Overview of milling techniques for improving the solubility of poorly water-soluble drugs","volume":"10","author":"Loh","year":"2015","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0378-5173(00)00516-0","article-title":"Effect of particle size, air flow and inhaler device on the aerosolisation of disodium cromoglycate powders","volume":"206","author":"Chew","year":"2000","journal-title":"Int. J. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ejps.2018.10.026","article-title":"Spray drying of pharmaceuticals and biopharmaceuticals: Critical parameters and experimental process optimization approaches","volume":"127","author":"Ziaee","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.apt.2013.09.012","article-title":"Formation of particles for dry powder inhalers","volume":"25","year":"2014","journal-title":"Adv. Powder Technol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.addr.2006.07.010","article-title":"Particle engineering techniques for inhaled biopharmaceuticals","volume":"58","author":"Shoyele","year":"2006","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s11095-006-9174-3","article-title":"Particle engineering for pulmonary drug delivery","volume":"24","author":"Chow","year":"2007","journal-title":"Pharm. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.jconrel.2021.03.033","article-title":"Electrospinning for drug delivery applications: A review","volume":"334","author":"Luraghi","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"014108","DOI":"10.1088\/1468-6996\/11\/1\/014108","article-title":"Electrospun nanofibrous materials for tissue engineering and drug delivery","volume":"11","author":"Cui","year":"2010","journal-title":"Sci. Technol. Adv. Mater."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ito, T., Yamazoe, E., and Tahara, K. (2022). Dry Powder Inhalers for Proteins Using Cryo-Milled Electrospun Polyvinyl Alcohol Nanofiber Mats. Molecules, 27.","DOI":"10.3390\/molecules27165158"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"122357","DOI":"10.1016\/j.ijpharm.2022.122357","article-title":"Pharmaceutical dry powders of small molecules prepared by thin-film freezing and their applications\u2013A focus on the physical and aerosol properties of the powders","volume":"629","author":"Praphawatvet","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"120215","DOI":"10.1016\/j.ijpharm.2021.120215","article-title":"Aerosolizable siRNA-encapsulated solid lipid nanoparticles prepared by thin-film freeze-drying for potential pulmonary delivery","volume":"596","author":"Wang","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pardeshi, S.R., Kole, E.B., Kapare, H.S., Chandankar, S.M., Shinde, P.J., Boisa, G.S., Salgaonkar, S.S., Giram, P.S., More, M.P., and Kolimi, P. (2022). Progress on Thin Film Freezing Technology for Dry Powder Inhalation Formulations. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122632"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tellier, R., Li, Y., Cowling, B.J., and Tang, J.W. (2019). Recognition of aerosol transmission of infectious agents: A commentary. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-3707-y"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8","DOI":"10.22159\/ajpcr.2017.v10i2.14282","article-title":"Advancements In Dry Powder Inhaler","volume":"10","year":"2017","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1007\/s12325-019-01066-6","article-title":"Understanding Dry Powder Inhalers: Key Technical and Patient Preference Attributes","volume":"36","author":"Levy","year":"2019","journal-title":"Adv. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1089\/jam.1991.4.151","article-title":"Dry powder inhalers: Advantages and limitations","volume":"4","author":"Crompton","year":"1991","journal-title":"J. Aerosol Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1183\/09031936.00187510","article-title":"Inhaled dry powder mannitol in cystic fibrosis: An efficacy and safety study","volume":"38","author":"Bilton","year":"2011","journal-title":"Eur. Respir. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3109\/02770903.2015.1099160","article-title":"Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting","volume":"53","author":"Westerik","year":"2016","journal-title":"J. Asthma"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.ijpharm.2009.07.002","article-title":"Understanding the effect of lactose particle size on the properties of DPI formulations using experimental design","volume":"380","author":"Guenette","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1208\/s12249-014-0166-z","article-title":"Evaluation of granulated lactose as a carrier for DPI formulations 1: Effect of granule size","volume":"15","author":"Du","year":"2014","journal-title":"AAPS PharmSciTech"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1007\/s13346-017-0462-8","article-title":"Agglomerated novel spray-dried lactose-leucine tailored as a carrier to enhance the aerosolization performance of salbutamol sulfate from DPI formulations","volume":"8","author":"Molina","year":"2018","journal-title":"Drug. Deliv. Transl. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1517\/17425247.1.1.67","article-title":"Dry powder inhalers for pulmonary drug delivery","volume":"1","author":"Frijlink","year":"2004","journal-title":"Expert Opin. Drug. Deliv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1615\/CritRevTherDrugCarrierSyst.2014010527","article-title":"Advanced aerosol delivery devices for potential cure of acute and chronic diseases","volume":"31","author":"Kaur","year":"2014","journal-title":"Crit. Rev. Ther. Drug. Carr. Syst."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1081\/DDC-100000238","article-title":"Deposition of nacystelyn from a dry powder inhaler in healthy volunteers and cystic fibrosis patients","volume":"27","author":"Vanderbist","year":"2001","journal-title":"Drug. Dev. Ind. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e000119","DOI":"10.1136\/bmjresp-2015-000119","article-title":"Evaluation of inhaler handling-errors, inhaler perception and preference with Spiromax, Easyhaler and Turbuhaler devices among healthy Finnish volunteers: A single site, single visit crossover study (Finhaler)","volume":"3","author":"Sandler","year":"2016","journal-title":"BMJ Open. Respir. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"16053","DOI":"10.1038\/npjpcrm.2016.53","article-title":"Difference in resistance to humidity between commonly used dry powder inhalers: An in vitro study","volume":"26","author":"Janson","year":"2016","journal-title":"NPJ Prim. Care Respir. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s41030-016-0025-z","article-title":"Budesonide\/Formoterol Easyhaler\u00ae: Performance Under Simulated Real-Life Conditions","volume":"3","author":"Haikarainen","year":"2017","journal-title":"Pulm. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1089\/jamp.2017.1416","article-title":"Peak Inspiratory Flow Rate in Chronic Obstructive Pulmonary Disease: Implications for Dry Powder Inhalers","volume":"30","author":"Ghosh","year":"2017","journal-title":"J. Aerosol Med. Pulm. Drug. Deliv."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1089\/jamp.2013.1119","article-title":"The inhalation characteristics of patients when they use different dry powder inhalers","volume":"28","author":"Azouz","year":"2015","journal-title":"J. Aerosol Med. Pulm. Drug. Deliv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1089\/jamp.2014.1132","article-title":"Inhaled drug delivery in the hands of the patient","volume":"27","author":"Lavorini","year":"2014","journal-title":"J. Aerosol Med. Pulm. Drug. Deliv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.rmed.2011.01.005","article-title":"Inhaler mishandling remains common in real life and is associated with reduced disease control","volume":"105","author":"Melani","year":"2011","journal-title":"Respir. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1067\/mpd.2001.112897","article-title":"Clinical outcome after early Pseudomonas aeruginosa infection in cystic fibrosis","volume":"138","author":"Nixon","year":"2001","journal-title":"J. Pediatr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1021\/acsptsci.0c00030","article-title":"Metabolomic Description of Ivacaftor Elevating Polymyxin B Mediated Antibacterial Activity in Cystic Fibrosis Pseudomonas aeruginosa","volume":"3","author":"Allobawi","year":"2020","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2217\/17460913.1.1.53","article-title":"Cystic fibrosis: A polymicrobial infectious disease","volume":"1","author":"Sibley","year":"2006","journal-title":"Future Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1021\/acsinfecdis.6b00035","article-title":"An \u201cUnlikely\u201d Pair: The Antimicrobial Synergy of Polymyxin B in Combination with the Cystic Fibrosis Transmembrane Conductance Regulator Drugs KALYDECO and ORKAMBI","volume":"2","author":"Schneider","year":"2016","journal-title":"ACS Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.biotechadv.2018.11.013","article-title":"Antibiotic resistance in Pseudomonas aeruginosa: Mechanisms and alternative therapeutic strategies","volume":"37","author":"Pang","year":"2019","journal-title":"Biotechnol. Adv."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1164\/rccm.201009-1478CI","article-title":"Managing cystic fibrosis: Strategies that increase life expectancy and improve quality of life","volume":"183","author":"Shoseyov","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1021\/acsinfecdis.7b00238","article-title":"Sputum Active Polymyxin Lipopeptides: Activity against Cystic Fibrosis Pseudomonas aeruginosa Isolates and Their Interactions with Sputum Biomolecules","volume":"4","author":"Paulin","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Harwood, K.H., McQuade, R.M., Jarnicki, A., and Schneider-Futschik, E.K. (2021). Anti-Inflammatory Influences of Cystic Fibrosis Transmembrane Conductance Regulator Drugs on Lung Inflammation in Cystic Fibrosis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22147606"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1021\/acsptsci.2c00007","article-title":"Ivacaftor Alters Macrophage and Lymphocyte Infiltration in the Lungs Following Lipopolysaccharide Exposure","volume":"5","author":"Harwood","year":"2022","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/01.JAA.0000515540.36581.92","article-title":"Keep them breathing: Cystic fibrosis pathophysiology, diagnosis, and treatment","volume":"30","author":"Brown","year":"2017","journal-title":"JAAPA"},{"key":"ref_63","first-page":"1662","article-title":"CFTR Modulators: The Changing Face of Cystic Fibrosis in the Era of Precision Medicine","volume":"10","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1002\/cpt.548","article-title":"Can Cystic Fibrosis Patients Finally Catch a Breath With Lumacaftor\/Ivacaftor?","volume":"101","author":"Schneider","year":"2017","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1513\/AnnalsATS.201802-075FR","article-title":"Cystic Fibrosis: Translating Molecular Mechanisms into Effective Therapies","volume":"15","author":"Jennings","year":"2018","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1164\/rccm.201404-0703OC","article-title":"Clinical mechanism of the cystic fibrosis transmembrane conductance regulator potentiator ivacaftor in G551D-mediated cystic fibrosis","volume":"190","author":"Rowe","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1021\/acsptsci.9b00060","article-title":"Emerging Cystic Fibrosis Transmembrane Conductance Regulator Modulators as New Drugs for Cystic Fibrosis: A Portrait of in Vitro Pharmacology and Clinical Translation","volume":"3","author":"Ghelani","year":"2020","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1182\/blood-2014-02-555268","article-title":"A neutrophil intrinsic impairment affecting Rab27a and degranulation in cystic fibrosis is corrected by CFTR potentiator therapy","volume":"124","author":"Pohl","year":"2014","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1513\/AnnalsATS.201609-689OC","article-title":"Lumacaftor\/Ivacaftor Treatment of Patients with Cystic Fibrosis Heterozygous for F508del-CFTR","volume":"14","author":"Rowe","year":"2017","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1056\/NEJMoa1807120","article-title":"VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles","volume":"379","author":"Keating","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_71","first-page":"192","article-title":"Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy","volume":"25","author":"Ridley","year":"2020","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1056\/NEJMoa1709846","article-title":"Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del","volume":"377","author":"Munck","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/S0140-6736(19)32597-8","article-title":"Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: A double-blind, randomised, phase 3 trial","volume":"394","author":"Heijerman","year":"2019","journal-title":"Lancet"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","article-title":"Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele","volume":"381","author":"Middleton","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1164\/rccm.201207-1160OE","article-title":"Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health","volume":"187","author":"Mogayzel","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_76","first-page":"CD002768","article-title":"Physical exercise training for cystic fibrosis","volume":"11","author":"Radtke","year":"2017","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"a009779","DOI":"10.1101\/cshperspect.a009779","article-title":"Antibiotic and anti-inflammatory therapies for cystic fibrosis","volume":"3","author":"Chmiel","year":"2013","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"00132-2020","DOI":"10.1183\/23120541.00132-2020","article-title":"Inhaled dry powder alginate oligosaccharide in cystic fibrosis: A randomised, double-blind, placebo-controlled, crossover phase 2b study","volume":"6","author":"Davies","year":"2020","journal-title":"ERJ Open. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/(SICI)1099-0496(199901)27:1<43::AID-PPUL9>3.0.CO;2-E","article-title":"Effects of standard and high doses of salmeterol on lung function of hospitalized patients with cystic fibrosis","volume":"27","author":"Hordvik","year":"1999","journal-title":"Pediatr. Pulmonol."},{"key":"ref_80","first-page":"448","article-title":"Nebulised antibiotherapy: Conventional versus nanotechnology-based approaches, is targeting at a nano scale a difficult subject?","volume":"5","author":"Ballesteros","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"179","DOI":"10.2147\/MDER.S16360","article-title":"Tobramycin administered by the TOBI\u00ae Podhaler\u00ae for persons with cystic fibrosis: A review","volume":"4","author":"VanDevanter","year":"2011","journal-title":"Med. Devices Evid. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"7271","DOI":"10.2147\/IDR.S318173","article-title":"Inhaled Colistimethate Sodium in the Management of Patients with Bronchiectasis Infected by Pseudomonas aeruginosa: A Narrative Review of Current Evidence","volume":"15","author":"Golpe","year":"2022","journal-title":"Infect. Drug. Resist."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e000100","DOI":"10.1136\/bmjresp-2015-000100","article-title":"Ciprofloxacin DPI: A randomised, placebo-controlled, phase IIb efficacy and safety study on cystic fibrosis","volume":"2","author":"Dorkin","year":"2015","journal-title":"BMJ Open. Respir. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.prrv.2007.02.009","article-title":"Mucolytics in cystic fibrosis","volume":"8","author":"Henke","year":"2007","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_85","first-page":"CD001127","article-title":"Dornase alfa for cystic fibrosis","volume":"9","author":"Yang","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_86","first-page":"CD001506","article-title":"Nebulised hypertonic saline for cystic fibrosis","volume":"9","author":"Wark","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_87","unstructured":"Hsu, E., and Bajaj, T. (2022). Beta 2 Agonists."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1378\/chest.08-1421","article-title":"Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis","volume":"135","author":"Quittner","year":"2009","journal-title":"Chest"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1136\/thoraxjnl-2012-202059","article-title":"Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: A randomised study","volume":"68","author":"Schuster","year":"2013","journal-title":"Thorax"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jcf.2006.10.010","article-title":"Dry powder inhalation of colistin in cystic fibrosis patients: A single dose pilot study","volume":"6","author":"Westerman","year":"2007","journal-title":"J. Cyst. Fibros."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"9793","DOI":"10.1093\/nar\/gky693","article-title":"Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature","volume":"46","author":"Poitevin","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1128\/AAC.44.12.3249-3256.2000","article-title":"Aminoglycosides: Perspectives on mechanisms of action and resistance and strategies to counter resistance","volume":"44","author":"Kotra","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e65836","DOI":"10.7554\/eLife.65836","article-title":"Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane","volume":"10","author":"Sabnis","year":"2021","journal-title":"eLife"},{"key":"ref_94","first-page":"373","article-title":"Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use","volume":"35","author":"Monk","year":"1988","journal-title":"Drugs"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s40261-013-0082-0","article-title":"Inhalation of a dry powder ciprofloxacin formulation in healthy subjects: A phase I study","volume":"33","author":"Stass","year":"2013","journal-title":"Clin. Drug. Investig."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.jcf.2017.02.003","article-title":"Inhaled dry powder mannitol in children with cystic fibrosis: A randomised efficacy and safety trial","volume":"16","author":"Haarman","year":"2017","journal-title":"J. Cyst. Fibros."},{"key":"ref_97","unstructured":"(CHMP) CfMPfHU (2009). Guideline on the Clinical Development of Medicinal Products for the Treatment of Cystic Fibrosis, European Medicines Agency."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1185\/03007995.2013.805122","article-title":"Tobramycin inhalation powder manufactured by improved process in cystic fibrosis: The randomized EDIT trial","volume":"29","author":"Galeva","year":"2013","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jcf.2010.10.003","article-title":"Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: The EAGER trial","volume":"10","author":"Konstan","year":"2011","journal-title":"J. Cyst. Fibros."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s40273-013-0122-x","article-title":"The cost effectiveness of dry powder antibiotics for the treatment of Pseudomonas aeruginosa in patients with cystic fibrosis","volume":"32","author":"Tappenden","year":"2014","journal-title":"Pharmacoeconomics"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1016\/j.clinthera.2013.08.003","article-title":"Tolerability and pharmacokinetic properties of ciprofloxacin dry powder for inhalation in patients with cystic fibrosis: A phase I, randomized, dose-escalation study","volume":"35","author":"Stass","year":"2013","journal-title":"Clin. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1164\/rccm.201109-1666OC","article-title":"Long-term inhaled dry powder mannitol in cystic fibrosis: An international randomized study","volume":"185","author":"Aitken","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1177\/1753465817710596","article-title":"Ease of use of tobramycin inhalation powder compared with nebulized tobramycin and colistimethate sodium: A crossover study in cystic fibrosis patients with pulmonary Pseudomonas aeruginosa infection","volume":"11","author":"Greenwood","year":"2017","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jconrel.2019.01.025","article-title":"Inhalation treatment of cystic fibrosis with lumacaftor and ivacaftor co-delivered by nanostructured lipid carriers","volume":"296","author":"Garbuzenko","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"121859","DOI":"10.1016\/j.ijpharm.2022.121859","article-title":"Spray dried inhalable ivacaftor co-amorphous microparticle formulations with leucine achieved enhanced in vitro dissolution and superior aerosol performance","volume":"622","author":"Guan","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/FPC.0000000000000246","article-title":"PharmGKB summary: Ivacaftor pathway, pharmacokinetics\/pharmacodynamics","volume":"27","author":"Fohner","year":"2017","journal-title":"Pharm. Genom."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/j.1476-5381.2010.01127.x","article-title":"Principles of early drug discovery","volume":"162","author":"Hughes","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"390","DOI":"10.3389\/fphar.2017.00390","article-title":"Personalized or Precision Medicine? The Example of Cystic Fibrosis","volume":"8","author":"Marson","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1126\/science.aaw0553","article-title":"Making precision medicine personal for cystic fibrosis","volume":"365","author":"Manfredi","year":"2019","journal-title":"Science"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1056\/NEJMoa0909825","article-title":"Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation","volume":"363","author":"Accurso","year":"2010","journal-title":"N. Engl. J. Med."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/5\/1488\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:34:24Z","timestamp":1760124864000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/5\/1488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,13]]},"references-count":110,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["pharmaceutics15051488"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15051488","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,13]]}}}