Generation of Tailored Aerosols for Inhalative Drug Delivery Employing Recent Vibrating-Mesh Nebulizer Systems

References

• Groneberg DA Witt C Wagner U Chung KF Fischer A . Fundamentals of pulmonary drug delivery. Respir. Med.97, 382–387 (2003).
   PubMed Web of Science ®Google Scholar
• Rau JL . The inhalation of drugs: advantages and problems. Respir. Care50, 367–382 (2005).
   PubMedGoogle Scholar
• Ruge CA Kirch J Lehr CM . Pulmonary drug delivery: from generating aerosols to overcoming biological barriers-therapeutic possibilities and technological challenges. Lancet Respir. Med.1, 402–413 (2013).
   PubMed Web of Science ®Google Scholar
• Hickey AJ . Controlled delivery of inhaled therapeutic agents. J. Control Release190, 182–188 (2014).
   PubMed Web of Science ®Google Scholar
• Chow AH Tong HH Chattopadhyay P Shekunov BY . Particle engineering for pulmonary drug delivery. Pharm. Res.24, 411–437 (2007).
   PubMed Web of Science ®Google Scholar
• Courrier HM Butz N Vandamme TF . Pulmonary drug delivery systems: recent developments and prospects. Crit. Rev. Ther. Drug Carrier Syst.19, 425–498 (2002).
   PubMed Web of Science ®Google Scholar
• Dolovich MB Dhand R . Aerosol drug delivery: developments in device design and clinical use. Lancet377, 1032–1045 (2011).
   PubMed Web of Science ®Google Scholar
• Heyder J . Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respiratory drug delivery. Proc. Am. Thorac. Soc.1, 315–320 (2004).
   PubMedGoogle Scholar
• Carvalho TC Peters JI Williams RO 3rd . Influence of particle size on regional lung deposition–what evidence is there?Int. J. Pharm.406, 1–10 (2011).
   PubMed Web of Science ®Google Scholar
• Hofmann W . Modelling inhaled particle deposition in the human lung–a review. J. Aerosol Sci.42, 693–724 (2011).
   Web of Science ®Google Scholar
• Anderson PJ . History of aerosol therapy: liquid nebulization to MDIs to DPIs. Respir. Care50, 1139–1150 (2005).
   PubMedGoogle Scholar
• Dhand R . Nebulizers that use a vibrating mesh or plate with multiple apertures to generate aerosol. Respir. Care47, 1406–1418 (2002).
   PubMedGoogle Scholar
• Steckel H Eskandar F . Factors affecting aerosol performance during nebulization with jet and ultrasonic nebulizers. Eur. J. Pharm. Sci.19, 443–455 (2003).
   PubMed Web of Science ®Google Scholar
• Waldrep JC Dhand R . Advanced nebulizer designs employing vibrating mesh/aperture plate technologies for aerosol generation. Curr. Drug Deliv.5, 114–119 (2008).
   PubMedGoogle Scholar
• Watts AB McConville JT Williams RO 3rd . Current therapies and technological advances in aqueous aerosol drug delivery. Drug Dev. Ind. Pharm.34, 913–922 (2008).
   PubMed Web of Science ®Google Scholar
• Beck-Broichsitter M Kleimann P Schmehl T et al. Impact of lyoprotectants for the stabilization of biodegradable nanoparticles on the performance of air-jet, ultrasonic, and vibrating-mesh nebulizers. Eur. J. Pharm. Biopharm.82, 272–280 (2012).
   PubMed Web of Science ®Google Scholar
• Zhou QT Tang P Leung SS Chan JG Chan HK . Emerging inhalation aerosol devices and strategies: where are we headed?Adv. Drug Deliv. Rev.75, 3–17 (2014).
   PubMed Web of Science ®Google Scholar
• Martin AR Finlay WH . Nebulizers for drug delivery to the lungs. Expert Opin. Drug Deliv. doi: 10.1517/17425247.174217995087 (2014) ( Epub ahead of print).
   PubMed Web of Science ®Google Scholar
• Ghazanfari T Elhissi AM Ding Z Taylor KM . The influence of fluid physicochemical properties on vibrating-mesh nebulization. Int. J. Pharm.339, 103–111 (2007).
   PubMed Web of Science ®Google Scholar
• Zhang G David A Wiedmann TS . Performance of the vibrating membrane aerosol generation device: Aeroneb micropump nebulizer. J. Aerosol Med.20, 408–416 (2007).
   PubMedGoogle Scholar
• Beck-Broichsitter M Knuedeler MC Seeger W Schmehl T . Controlling the droplet size of formulations nebulized by vibrating-membrane technology. Eur. J. Pharm. Biopharm.87, 524–529 (2014).
   PubMed Web of Science ®Google Scholar
• Yu J Chien YW . Pulmonary drug delivery: physiologic and mechanistic aspects. Crit. Rev. Ther. Drug Carrier Syst.14, 395–453 (1997).
   PubMed Web of Science ®Google Scholar
• Labiris NR Dolovich MB . Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br. J. Clin. Pharmacol.56, 588–599 (2003).
   PubMed Web of Science ®Google Scholar
• Cone RA . Barrier properties of mucus. Adv. Drug Deliv. Rev.61, 75–85 (2009).
   PubMed Web of Science ®Google Scholar
• Fahy JV Dickey BF . Airway mucus function and dysfunction. N. Engl. J. Med.363, 2233–2247 (2010).
   PubMed Web of Science ®Google Scholar
• Lopez-Rodriguez E Perez-Gil J . Structure-function relationships in pulmonary surfactant membranes: from biophysics to therapy. Biochim. Biophys. Acta1838 (6), 1568–1585 (2014).
   PubMed Web of Science ®Google Scholar
• Parra E Perez-Gil J . Composition, structure and mechanical properties define performance of pulmonary surfactant membranes and films. Chem. Phys. Lipids185, 153–175 (2015).
   PubMed Web of Science ®Google Scholar
• Gehr P Green F Geiser M Im Hof V Lee NM Schürch S . Airway surfactant, a primary defense barrier: mechanical and immunological aspects. J. Aerosol Med.9, 163–181 (1996).
   PubMedGoogle Scholar
• Geiser M . Update on macrophage clearance of inhaled micro- and nanoparticles. J. Aerosol Med.23, 207–217 (2010).
   Google Scholar
• Rudolf G Köbrich R Stahlhofen W James AC . Regional aerosol deposition in man - a statistical and algebraic model. Ann. Occup. Hyg.38 (S1), 1–14 (1994).
   Google Scholar
• Roth AP Lange CF Finlay WH . The effect of breathing pattern on nebulizer drug delivery. J. Aerosol Med.16, 325–339 (2003).
   PubMedGoogle Scholar
• Cheng YS . Mechanisms of pharmaceutical aerosol deposition in the respiratory tract. AAPS PharmSciTech.15, 630–640 (2014).
   PubMed Web of Science ®Google Scholar
• Heyder J Gebhart J Rudolf G Schiller CF Stahlhofen W . Deposition of particles in the human respiratory tract in the size range 0.005–015 µm. J. Aerosol Sci.17, 811–825 (1986).
   Web of Science ®Google Scholar
• Schiller CF Gebhardt J Heyder J Rudolf G Stahlhofen W . Deposition of monodisperse insoluble aerosol particles in the 0.005 to 0.2 µm size range within the human respiratory tract. Ann. Occup. Hyg.32, 41–49 (1988).
   Google Scholar
• Beck-Broichsitter M Merkel OM Kissel T . Controlled pulmonary drug and gene delivery using polymeric nano-carriers. J. Control Release161, 214–224 (2012).
   PubMed Web of Science ®Google Scholar
• Finlay WH Martin AR . Recent advances in predictive understanding of respiratory tract deposition. J. Aerosol Med.21, 189–205 (2008).
   Google Scholar
• Finlay WH . Estimating the type of hygroscopic behavior exhibited by aqueous droplets. J. Aerosol Med.11, 221–229 (1998).
   PubMedGoogle Scholar
• Finlay WH Stapleton KW Zuberbuhler P . Errors in regional lung deposition predictions of nebulized salbutamol sulphate due to neglect or partial inclusion of hygroscopic effects. Int. J. Pharm.149, 63–72 (1997).
   Web of Science ®Google Scholar
• Finlay WH Stapleton KW Chan HK Zuberbuhler P Gonda I . Regional deposition of inhaled hygroscopic aerosols: in vivo SPECT compared with mathematical modeling. J. Appl. Physiol.81, 374–383 (1996).
   PubMed Web of Science ®Google Scholar
• Fleming JS Epps BP Conway JH Martonen TB . Comparison of SPECT aerosol deposition data with a human respiratory tract model. J. Aerosol Med.19, 268–278 (2006).
   PubMedGoogle Scholar
• Patton JS Brain JD Davies LA et al. The particle has landed-characterizing the fate of inhaled pharmaceuticals. J. Aerosol Med.23, S71–S87 (2010).
   Google Scholar
• de Souza Carvalho C Daum N Lehr CM . Carrier interactions with the biological barriers of the lung: advanced in vitro models and challenges for pulmonary drug delivery. Adv. Drug Deliv. Rev.75, 129–140 (2014).
   PubMed Web of Science ®Google Scholar
• Cazzola M Rogliani P Novelli L Matera MG . Inhaled corticosteroids for chronic obstructive pulmonary disease. Expert Opin. Pharmacother.14, 2489–2499 (2013).
   PubMed Web of Science ®Google Scholar
• Louie S Zeki AA Schivo M et al. The asthma-chronic obstructive pulmonary disease overlap syndrome: pharmacotherapeutic considerations. Expert Rev. Clin. Pharmacol.6, 197–219 (2013).
   PubMed Web of Science ®Google Scholar
• Ehrick JD Wylie J Goodey AP Li Y Liu O Donovan B . Orally inhaled fixed-dose combination products for the treatment of asthma and chronic obstructive pulmonary disease: not simple math. Ther. Deliv.5, 297–317 (2014).
   PubMedGoogle Scholar
• Scheuch G Kohlhaeufl MJ Brand P Siekmeier R . Clinical perspectives on pulmonary systemic and macromolecular delivery. Adv. Drug Deliv. Rev.58, 996–1008 (2006).
   PubMed Web of Science ®Google Scholar
• Patton JS Byron PR . Inhaling medicines: delivering drugs to the body through the lungs. Nat. Rev. Drug Discov.6, 67–74 (2007).
   PubMed Web of Science ®Google Scholar
• Hickey AJ . Back to the future: inhaled drug products. J. Pharm. Sci.102, 1165–1172 (2013).
   PubMed Web of Science ®Google Scholar
• Mortensen NP Hickey AJ . Targeting inhaled therapy beyond the lungs. Respiration88, 353–354 (2014).
   PubMed Web of Science ®Google Scholar
• Schürch S Gehr P Im Hof V Geiser M Green F . Surfacntant displaces particles toward the epithelium in airways and alveoli. Respir. Physiol.80, 17–32 (1990).
   PubMedGoogle Scholar
• Geiser M Schurch S Gehr P . Influence of surface chemistry and topography of particles on their immersion into the lung's surface-lining layer. J. Appl. Physiol.94, 1793–1801 (2003).
   PubMed Web of Science ®Google Scholar
• Lai SK Wang YY Wirtz D Hanes J . Micro- and macrorheology of mucus. Adv. Drug Deliv. Rev.61, 86–100 (2009).
   PubMed Web of Science ®Google Scholar
• Sanders N Rudolph C Braeckmans K De Smedt SC Demeester J . Extracellular barriers in respiratory gene therapy. Adv. Drug Deliv. Rev.61, 115–127 (2009).
   PubMed Web of Science ®Google Scholar
• van der Schans CP . Bronchial mucus transport. Respir. Care52, 1150–1158 (2007).
   PubMed Web of Science ®Google Scholar
• Ruge CA Kirch J Canadas O et al. Uptake of nanoparticles by alveolar macrophages is triggered by surfactant protein A. Nanomedicine7, 690–693 (2011).
   PubMed Web of Science ®Google Scholar
• Schleh C Rothen-Rutishauser BM Blank F et al. Surfactant protein D modulates allergen particle uptake and inflammatory response in a human epithelial airway model. Respir. Res.13, 8 (2012).
   PubMed Web of Science ®Google Scholar
• Gradon L Podgorski A . Hydrodynamical model of pulmonary clearance. Chem. Eng. Sci.44, 741–749 (1989).
   Web of Science ®Google Scholar
• Sosnowski TR Gradon L Podgorski A . Influence of insoluble aerosol deposits on the surface activity of the pulmonary surfactant: a possible mechanism of alveolar clearance retardation?Aerosol Sci. Technol.32, 52–60 (2000).
   Web of Science ®Google Scholar
• Brown RA Schanker LS . Absorption of aerosolized drugs from the rat lung. Drug Metab. Dispos.11, 355–360 (1983).
   PubMed Web of Science ®Google Scholar
• Tronde A Norden B Jeppsson AB et al. Drug absorption from the isolated perfused rat lung - correlations with drug physicochemical properties and epithelial permeability. J. Drug Target11, 61–74 (2003).
   PubMed Web of Science ®Google Scholar
• Wiedmann TS Bhatia R Wattenberg LW . Drug solubilization in lung surfactant. J. Control Release65, 43–47 (2000).
   PubMed Web of Science ®Google Scholar
• Ibrahim M Garcia-Contreras L . Mechanisms of absorption and elimination of drugs administered by inhalation. Ther. Deliv.4, 1027–1045 (2013).
   PubMedGoogle Scholar
• Bayard FJ Thielemans W Pritchard DI et al. Polyethylene glycol-drug ester conjugates for prolonged retention of small inhaled drugs in the lung. J. Control Release171, 234–240 (2013).
   PubMed Web of Science ®Google Scholar
• Zhang JY Wang Y Prakash C . Xenobiotic-metabolizing enzymes in human lung. Curr. Drug Metab.7, 939–948 (2006).
   PubMed Web of Science ®Google Scholar
• Baginski L Tachon G Falson F Patton JS Bakowsky U Ehrhardt C . Reverse transcription polymerase chain reaction (RT-PCR) analysis of proteolytic enzymes in cultures of human respiratory epithelial cells. J. Aerosol Med.24, 89–101 (2011).
   Google Scholar
• Wang YB Watts AB Peters JI Williams RO 3rd . The impact of pulmonary diseases on the fate of inhaled medicines-a review. Int. J. Pharm.461, 112–128 (2014).
   PubMed Web of Science ®Google Scholar
• Postma DS Reddel HK ten Hacken NH van den Berge M . Asthma and chronic obstructive pulmonary disease: similarities and differences. Clin. Chest Med.35, 143–156 (2014).
   PubMed Web of Science ®Google Scholar
• Matthay MA Zemans RL . The acute respiratory distress syndrome: pathogenesis and treatment. Ann. Rev. Pathol.6, 147–163 (2011).
   PubMed Web of Science ®Google Scholar
• Kim CS Kang TC . Comparative measurements of lung deposition of inhaled fine particles in normal subjects and patients with obstructive airway disease. Am. J. Respir. Crit. Care Med.155, 899–905 (1997).
   PubMed Web of Science ®Google Scholar
• Geller DE . Comparing clinical features of the nebulizer, metered-dose inhaler, and dry powder inhaler. Respir. Care50, 1313–1322 (2005).
   PubMedGoogle Scholar
• Sanchis J Corrigan C Levy ML et al. Inhaler devices–from theory to practice. Respir. Med.107, 495–502 (2013).
   PubMed Web of Science ®Google Scholar
• Newman SP . Principles of metered-dose inhaler design. Respir. Care50, 1177–1190 (2005).
   PubMedGoogle Scholar
• Smyth HD . Propellant-driven metered-dose inhalers for pulmonary drug delivery. Expert Opin. Drug Deliv.2, 53–74 (2005).
   PubMedGoogle Scholar
• Bell J Newman S . The rejuvenated pressurised metered dose inhaler. Expert Opin. Drug Deliv.4, 215–234 (2007).
   PubMed Web of Science ®Google Scholar
• Ivey JW Vehring R Finlay WH . Understanding pressurized metered dose inhaler performance. Expert Opin. Drug Deliv. doi: 10.1517/17425247.174217984683 (2014) ( Epub ahead of print).
   PubMed Web of Science ®Google Scholar
• Rubin BK Fink JB . Optimizing aerosol delivery by pressurized metered-dose inhalers. Respir. Care50, 1191–1200 (2005).
   PubMedGoogle Scholar
• Dalby R Spallek M Voshaar T . A review of the development of Respimat Soft Mist Inhaler. Int. J. Pharm.283, 1–9 (2004).
   PubMed Web of Science ®Google Scholar
• Hochrainer D Hölz H Kreher C Scaffidi L Spallek M Wachtel H . Comparison of the aerosol velocity and spray duration of Respimat Soft Mist inhaler and pressurized metered dose inhalers. J. Aerosol Med.18, 273–282 (2005).
   PubMedGoogle Scholar
• Cordts E Steckel H . Formulation considerations for dry powder inhalers. Ther. Deliv.5, 675–689 (2014).
   PubMedGoogle Scholar
• Yang MY Chan JG Chan HK . Pulmonary drug delivery by powder aerosols. J. Control Release193, 228–240 (2014).
   PubMed Web of Science ®Google Scholar
• Hoppentocht M Hagedoorn P Frijlink HW de Boer AH . Technological and practical challenges of dry powder inhalers and formulations. Adv. Drug Deliv. Rev.75, 18–31 (2014).
   PubMed Web of Science ®Google Scholar
• Le Brun PP de Boer AH Heijerman HG Frijlink HW . A review of the technical aspects of drug nebulization. Pharm. World Sci.22, 75–81 (2000).
   PubMed Web of Science ®Google Scholar
• O'Callaghan C Barry PW . The science of nebulised drug delivery. Thorax52, S31–S44 (1997).
   PubMed Web of Science ®Google Scholar
• Rau JL . Design principles of liquid nebulization devices currently in use. Respir. Care47, 1257–1278 (2002).
   PubMedGoogle Scholar
• Westerman EM Heijerman HG Frijlink HW . Dry powder inhalation versus wet nebulisation delivery of antibiotics in cystic fibrosis patients. Expert Opin. Drug Deliv.4, 91–94 (2007).
   PubMed Web of Science ®Google Scholar
• Claus S Weiler C Schiewe J Friess W . How can we bring high drug doses to the lung?Eur. J. Pharm. Biopharm.86, 1–6 (2014).
   PubMed Web of Science ®Google Scholar
• Tiddens HA Bos AC Mouton JW Devadason S Janssens HM . Inhaled antibiotics: dry or wet?Eur. Respir. J.44, 1308–1318 (2014).
   PubMed Web of Science ®Google Scholar
• McCallion ONM Taylor KMG Bridges PA Thomas M Taylor AJ . Jet nebulizers for pulmonary drug delivery. Int. J. Pharm.130, 1–11 (1996).
   Web of Science ®Google Scholar
• Taylor KMG McCallion ONM . Ultrasonic nebulizers for pulmonary drug delivery. Int. J. Pharm.153, 93–104 (1997).
   Web of Science ®Google Scholar
• Yeo LY Friend JR McIntosh MP Meeusen ENT Morton DAV . Ultrasonic nebulization platforms for pulmonary drug delivery. Expert Opin. Drug Deliv.7, 663–679 (2010).
   PubMed Web of Science ®Google Scholar
• Gessler T Schmehl T Hoeper MM et al. Ultrasonic versus jet nebulization of iloprost in severe pulmonary hypertension. Eur. Respir. J.17, 14–19 (2001).
   PubMed Web of Science ®Google Scholar
• Rau JL Ari A Restrepo RD . Performance comparison of nebulizer designs: constant-output, breath-enhanced, and dosimetric. Respir. Care49, 174–179 (2004).
   PubMedGoogle Scholar
• Hertel SP Winter G Friess W . Protein stability in pulmonary drug delivery via nebulization. Adv. Drug Deliv. Rev. doi: 10.1016/j.addr.1010.1003 (2014) ( Epub ahead of print).
   PubMed Web of Science ®Google Scholar
• O'Riordan TG . Formulations and nebulizer performance. Respir. Care47, 1305–1313 (2002).
   PubMedGoogle Scholar
• McCallion ONM Taylor KMG Thomas M Taylor AJ . Nebulization of fluids of different physicochemical properties with air-jet and ultrasonic nebulizers. Pharm. Res.12, 1682–1688 (1995).
   PubMed Web of Science ®Google Scholar
• McCallion ONM Patel MJ . Viscosity effects on nebulisation of aqueous solutions. Int. J. Pharm.130, 245–249 (1996).
   Web of Science ®Google Scholar
• McCallion ONM Taylor KMG Thomas M Taylor AJ . The influence of surface tension on aerosols produced by medical nebulisers. Int. J. Pharm.129, 123–126 (1996).
   Web of Science ®Google Scholar
• McCallion ONM Taylor KMG Thomas M Taylor AJ . Nebulisation of monodisperse latex sphere suspensions in air-jet and ultrasonic nebulisers. Int. J. Pharm.133, 203–214 (1996).
   Web of Science ®Google Scholar
• Najlah M Parveen I Alhnan MA et al. The effects of suspension particle size on the performance of air-jet, ultrasonic and vibrating-mesh nebulisers. Int. J. Pharm.461, 234–241 (2014).
   PubMed Web of Science ®Google Scholar
• Gaspar MM Bakowsky U Ehrhardt C . Inhaled liposomes - Current strategies and future challenges. J. Biomed. Nanotechnol.4, 245–257 (2008).
   Web of Science ®Google Scholar
• Cipolla D Gonda I Chan HK . Liposomal formulations for inhalation. Ther. Deliv.4, 1047–1072 (2013).
   PubMedGoogle Scholar
• Kurmi BD Kayat J Gajbhiye V Tekade RK Jain NK . Micro- and nano-carrier-mediated lung targeting. Expert Opin. Drug Deliv.7, 781–794 (2010).
   PubMed Web of Science ®Google Scholar
• Lebhardt T Roesler S Beck-Broichsitter M Kissel T . Polymeric nanocarriers for drug delivery to the lung. J. Drug Del. Sci. Tech.20, 171–180 (2010).
   Web of Science ®Google Scholar
• Dailey LA Kleemann E Wittmar M et al. Surfactant-free, biodegradable nanoparticles for aerosol therapy based on the branched polyesters, DEAPA-PVAL-g-PLGA. Pharm. Res.20, 2011–2020 (2003).
   PubMed Web of Science ®Google Scholar
• Dailey LA Schmehl T Gessler T et al. Nebulization of biodegradable nanoparticles: impact of nebulizer technology and nanoparticle characteristics on aerosol features. J. Control Release86, 131–144 (2003).
   PubMed Web of Science ®Google Scholar
• Dailey LA Kleemann E Merdan T et al. Modified polyethylenimines as non viral gene delivery systems for aerosol therapy: effects of nebulization on cellular uptake and transfection efficiency. J. Control Release100, 425–436 (2004).
   PubMed Web of Science ®Google Scholar
• Kleemann E Dailey LA Abdelhady HG et al. Modified polyethylenimines as non-viral gene delivery systems for aerosol gene therapy: investigations of the complex structure and stability during air-jet and ultrasonic nebulization. J. Control Release100, 437–450 (2004).
   PubMed Web of Science ®Google Scholar
• Elhissi AMA Taylor KMG . Delivery of liposomes generated from proliposomes using air-jet, ultrasonic, and vibrating-mesh nebulisers. J. Drug Deliv. Sci. Technol.15, 261–265 (2005).
   Web of Science ®Google Scholar
• Elhissi AMA Faizi M Naji WF Gill HS Taylor KMG . Physical stability and aerosol properties of liposomes delivered using an air-jet nebulizer and a novel micropump device with large mesh apertures. Int. J. Pharm.334, 62–70 (2007).
   PubMed Web of Science ®Google Scholar
• Zaru M Mourtas S Klepetsanis P Fadda AM Antimisiaris SG . Liposomes for drug delivery to the lungs by nebulization. Eur. J. Pharm. Biopharm.67, 655–666 (2007).
   PubMed Web of Science ®Google Scholar
• Kleemann E Schmehl T Gessler T Bakowsky U Kissel T Seeger W . Iloprost-containing liposomes for aerosol application in pulmonary arterial hypertension: formulation aspects and stability. Pharm. Res.24, 277–287 (2007).
   PubMed Web of Science ®Google Scholar
• Hureaux J Lagarce F Gagnadoux F et al. Lipid nanocapsules: ready-to-use nanovectors for the aerosol delivery of paclitaxel. Eur. J. Pharm. Biopharm.73, 239–246 (2009).
   PubMed Web of Science ®Google Scholar
• Elhissi AMA Giebultowicz J Stec AA et al. Nebulization of ultradeformable liposomes: the influence of aerosolization mechanism and formulation excipients. Int. J. Pharm.436, 519–526 (2012).
   PubMed Web of Science ®Google Scholar
• Beck-Broichsitter M Knuedeler MC Schmehl T Seeger W . Following the concentration of polymeric nanoparticles during nebulization. Pharm. Res.30, 16–24 (2013).
   PubMed Web of Science ®Google Scholar
• Geller DE . New liquid aerosol generation devices: systems that force pressurized liquids through nozzles. Respir. Care47, 1392–1405 (2002).
   PubMedGoogle Scholar
• Knoch M Keller M . The customised electronic nebuliser: a new category of liquid aerosol drug delivery system. Expert Opin. Drug Deliv.2, 377–390 (2005).
   PubMedGoogle Scholar
• Lass JS Sant A Knoch M . New advances in aerosolised drug delivery: vibrating membrane nebuliser technology. Expert Opin. Drug Deliv.3, 693–702 (2006).
   PubMedGoogle Scholar
• Katial RK Reisner C Buchmeier A Bartelson BB Nelson HS . Comparison of three commercial ultrasonic nebulizers. Ann. Allergy Asthma Immunol.84, 255–261 (2000).
   PubMed Web of Science ®Google Scholar
• Johnson JC Waldrep JC Guo J Dhand R . Aerosol delivery of recombinant human DNase I: in vitro comparison of a vibrating-mesh nebulizer with a jet nebulizer. Respir. Care53, 1703–1708 (2008).
   PubMed Web of Science ®Google Scholar
• Skaria S Smaldone GC . Omron NE U22: comparison between vibrating mesh and jet nebulizer. J. Aerosol Med.23, 173–180 (2010).
   Google Scholar
• Kohno M Matsuoka Y . Microfabrication and drilling using diffraction-free pulsed laser beam generated axicon lens. JSME Int. J. Ser. B47, 497–500 (2004).
   Web of Science ®Google Scholar
• Geerken MJ Groenendijk MNW Lammertink RGH Wessling M . Micro-fabricated metal nozzle plates used for water-in-oil and oil-in-water emulsification. J. Memb. Sci.310, 374–383 (2008).
   Web of Science ®Google Scholar
• Shen SC Wang YJ Chen YY . Design and fabrication of medical micro-nebulizers. Sens. Actuators A144, 135–143 (2008).
   Web of Science ®Google Scholar
• Lin CY Meng HC Fu C . An ultrasonic aerosol therapy nebulizer using electroformed palladium-nickel alloy nozzle plates. Sens. Actuators A169, 187–193 (2011).
   Web of Science ®Google Scholar
• Waldrep JC Berlinski A Dhand R . Comparative analysis of methods to measure aerosols generated by a vibrating mesh nebulizer. J. Aerosol Med.20, 310–319 (2007).
   PubMedGoogle Scholar
• Hertel S Pohl T Friess W Winter G . That's cool!-Nebulization of thermolabile proteins with a cooled vibrating mesh nebulizer. Eur. J. Pharm. Biopharm.87, 357–365 (2014).
   PubMed Web of Science ®Google Scholar
• Hertel S Pohl T Friess W Winter G . Prediction of protein degradation during vibrating mesh nebulization via a high throughput screening method. Eur. J. Pharm. Biopharm.87, 386–394 (2014).
   PubMed Web of Science ®Google Scholar
• Germershaus O Schultz I Lühmann T Beck-Broichsitter M Högger P Meinel L . Insulin-like growth factor-I aerosol formulations for pulmonary delivery. Eur. J. Pharm. Biopharm.85, 61–68 (2013).
   PubMed Web of Science ®Google Scholar
• Wagner A Vorauer-Uhl K Katinger H . Nebulization of liposomal rh-Cu/Zn-SOD with a novel vibrating membrane nebulizer. J. Liposome Res.16, 113–125 (2006).
   PubMed Web of Science ®Google Scholar
• Behr J Zimmermann G Baumgartner R et al. Lung deposition of a liposomal cyclosporine A inhalation solution in patients after lung transplantation. J. Aerosol Med.22, 121–129 (2009).
   Google Scholar
• Gaspar MM Gobbo O Ehrhardt C . Generation of liposome aerosols with the Aeroneb Pro and the AeroProbe nebulizers. J. Liposome Res.20, 55–61 (2010).
   PubMed Web of Science ®Google Scholar
• Beck-Broichsitter M Rieger M Reul R Gessler T Seeger W Schmehl T . Correlation of drug release with pulmonary drug absorption profiles for nebulizable liposomal formulations. Eur. J. Pharm. Biopharm.84, 106–114 (2013).
   PubMed Web of Science ®Google Scholar
• Lynch J Behan N Birkinshaw C . Factors controlling particle size during nebulization of DNA-polycation complexes. J. Aerosol Med.20, 257–268 (2007).
   PubMedGoogle Scholar
• Nguyen J Reul R Betz T et al. Nanocomposites of lung surfactant and biodegradable cationic nanoparticles improve transfection efficiency to lung cells. J. Control Release140, 47–54 (2009).
   PubMed Web of Science ®Google Scholar
• Beck-Broichsitter M Gauss J Packhaeuser CB et al. Pulmonary drug delivery with aerosolizable nanoparticles in an ex vivo lung model. Int. J. Pharm.367, 169–178 (2009).
   PubMed Web of Science ®Google Scholar
• Beck-Broichsitter M Kleimann P Gessler T Seeger W Kissel T Schmehl T . Nebulization performance of biodegradable sildenafil-loaded nanoparticles using the Aeroneb® Pro: formulation aspects and nanoparticle stability to nebulization. Int. J. Pharm.422, 398–408 (2012).
   PubMed Web of Science ®Google Scholar
• Beck-Broichsitter M Knuedeler MC Oesterheld N Seeger W Schmehl T . Boosting the aerodynamic properties of vibrating-mesh nebulized polymeric nanosuspensions. Int. J. Pharm.459, 23–29 (2014).
   PubMed Web of Science ®Google Scholar
• Li Z Zhang Y Wurtz W et al. Characterization of nebulized liposomal amikacin (Arikace) as a function of droplet size. J. Aerosol Med.21, 245–254 (2008).
   Google Scholar
• Waters V Ratjen F . Inhaled liposomal amikacin. Expert Rev. Respir. Med.8, 401–409 (2014).
   PubMed Web of Science ®Google Scholar
• Beck-Broichsitter M Schmehl T Seeger W . Customized vibrating-membrane nozzles for enhanced fluid atomization. Aerosol Sci. Technol.49iii–viii (2015).
   Web of Science ®Google Scholar
• Arzhavitina A Steckel H . Surface active drugs significantly alter the drug output rate from medical nebulizers. Int. J. Pharm.384, 128–136 (2010).
   PubMedGoogle Scholar
• Baumann R Glöckl G Nagel S Weitschies W . Preparation and characterization of magnetizable aerosols. Eur. J. Pharm. Sci.45, 693–697 (2012).
   PubMed Web of Science ®Google Scholar
• Najlah M Vali A Taylor M et al. A study of the effects of sodium halides on the performance of air-jet and vibrating-mesh nebulizers. Int. J. Pharm.456, 520–527 (2013).
   PubMed Web of Science ®Google Scholar
• Beck-Broichsitter M Oesterheld N Knuedeler MC Seeger W Schmehl T . On the correlation of output rate and aerodynamic characteristics in vibrating-mesh-based aqueous aerosol delivery. Int. J. Pharm.461, 34–37 (2014).
   PubMed Web of Science ®Google Scholar
• Beck-Broichsitter M Prüfer N Oesterheld N Seeger W Schmehl T . Nebulization of active pharmaceutical ingredients with the eFlow®rapid: impact of formulation variables on aerodynamic characteristics. J. Pharm. Sci.103, 2585–2589 (2014).
   PubMed Web of Science ®Google Scholar
• Olivier BJ Sorensen CM Taylor TW . Scaling dynamics of aerosol coagulation. Phys. Rev. A45, 5614–5623 (1992).
   PubMed Web of Science ®Google Scholar
• Garrett BC . Ions at the air/water interface. Science303, 1146–1147 (2004).
   PubMed Web of Science ®Google Scholar
• Ghosal S Hemminger JC Bluhm H et al. Electron spectroscopy of aqueous solution interfaces reveals surface enhancement of halides. Science307, 563–566 (2005).
   PubMed Web of Science ®Google Scholar
• Jungwirth P Tobias DJ . Specific ion effects at the air/water interface. Chem. Rev.106, 1259–1281 (2006).
   PubMed Web of Science ®Google Scholar
• Dalla-Bona AC Schmehl T Gessler T Seeger W Beck-Broichsitter M . Systematic aging of degradable nanosuspension ameliorates vibrating-mesh nebulizer performance. Drug Dev. Ind. Pharm. doi: 10.3109/03639045.036303993399 (2014) ( Epub ahead of print).
   PubMed Web of Science ®Google Scholar
• Weers JG Bell J Chan HK et al. Pulmonary formulations: what remains to be done? J. Aerosol Med. 23, S5–S23 (2010).
   Google Scholar
• Forbes B Asgharian B Dailey LA et al. Challenges in inhaled product development and opportunities for open innovation. Adv. Drug Deliv. Rev.63, 69–87 (2011).
   PubMed Web of Science ®Google Scholar
• Pilcer G Amighi K . Formulation strategy and use of excipients in pulmonary drug delivery. Int. J. Pharm.392, 1–19 (2010).
   PubMed Web of Science ®Google Scholar
• Fischer A Stegemann J Scheuch G Siekmeier R . Novel devices for individualized controlled inhalation can optimize aerosol therapy in efficacy, patient care and power of clinical trials. Eur. J. Med. Res.14, 71–77 (2009).
   PubMed Web of Science ®Google Scholar
• Denyer J Dyche T . The Adaptive Aerosol Delivery (AAD) technology: Past, present, and future. J. Aerosol Med.23, S1–S10 (2010).
   Google Scholar
• Denyer J Nikander K Smith NJ . Adaptive Aerosol Delivery (AAD) technology. Expert Opin. Drug Deliv.1, 165–176 (2004).
   PubMedGoogle Scholar
• Newman S . Improving inhaler technique, adherence to therapy and the precision of dosing: major challenges for pulmonary drug delivery. Expert Opin. Drug Deliv.11, 365–378 (2014).
   PubMed Web of Science ®Google Scholar