title: Boosting the aerodynamic properties of vibrating-mesh nebulized polymeric nanosuspensions.
abstract: Pulmonary application of drug-loaded polymeric nanosuspensions is achieved by vibrating-mesh nebulizers, which allow for an output of intact nanocarriers from the nebulizer reservoir. However, adequate aerosol droplet sizes are a prerequisite for an efficient pulmonary deposition. The current study discloses experimental findings useful to optimize the aerodynamic characteristics of formulations atomized by the vibrating-mesh nebulizers Aeroneb(®) Pro and eFlow(®)rapid. Parameters with significant influence on the aerosol droplet diameter were identified by a statistical design analysis rating size results from laser diffraction. Subsequently, the effect of selected biocompatible solutes on the aerodynamic performance of nebulized formulations was studied and correlated with their physicochemical properties. Vibrating-mesh generated aerosols were significantly affected by the dynamic viscosity and conductivity of the applied formulation. Consequently, an increase in viscosity enhancer (sucrose and poly(ethylene glycol)) or electrolyte (NaCl and CaCl2) content caused the droplet diameter to decrease. Similarly, purified nanosuspensions revealed a considerable decline in aerosol particle size upon excipient addition. However, coating of polymeric nanoparticles with poloxamer and poly(vinyl alcohol) was necessary to avoid electrolyte-induced nanoparticle aggregation. Overall, the current study emphasizes that supplementation of nanosuspensions with biocompatible solutes is an excellent means to tailor the characteristics of aerosols generated by vibrating-mesh technology.
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Klinikstrasse 33, D-35392 Giessen, Germany. Electronic address: moritz.beck-broichsitter@innere.med.uni-giessen.de.
authors.forename: Moritz
authors.initials: M
authors.lastname: Beck-Broichsitter
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Klinikstrasse 33, D-35392 Giessen, Germany.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Knuedeler
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Klinikstrasse 33, D-35392 Giessen, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Oesterheld
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Klinikstrasse 33, D-35392 Giessen, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität, Klinikstrasse 33, D-35392 Giessen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmehl
mesh_terms: D000327:Adsorption; D000336:Aerosols; D002626:Chemistry, Pharmaceutical; D003102:Colloids / Q000737:chemistry; D004337:Drug Carriers; D005079:Excipients; D019344:Lactic Acid; D053758:Nanoparticles; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D020442:Poloxamer; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D013501:Surface-Active Agents; D013535:Suspensions; D014732:Vibration
chemical_list: D000336:Aerosols; D003102:Colloids; D004337:Drug Carriers; D005079:Excipients; D011108:Polymers; D013501:Surface-Active Agents; D013535:Suspensions; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Aerosol; Biocompatible solutes; Biodegradable nanoparticles; Droplet size manipulation; Pulmonary drug delivery; Vibrating-mesh nebulization