title: Nebulization performance of biodegradable sildenafil-loaded nanoparticles using the Aeroneb Pro: formulation aspects and nanoparticle stability to nebulization.
abstract: Polymeric nanoparticles meet the increasing interest for drug delivery applications and hold great promise to improve controlled drug delivery to the lung. Here, we present a series of investigations that were carried out to understand the impact of formulation variables on the nebulization performance of novel biodegradable sildenafil-loaded nanoparticles designed for targeted aerosol therapy of life-threatening pulmonary arterial hypertension. Narrowly distributed poly(D,L-lactide-co-glycolide) nanoparticles (size: ∼200 nm) were prepared by a solvent evaporation technique using poly(vinyl alcohol) (PVA) as stabilizer. The aerodynamic and output characteristics using the Aeroneb Pro nebulizer correlated well with the dynamic viscosity of the employed fluids for nebulization. The nebulization performance was mainly affected by the amount of employed stabilizer, rather than by the applied nanoparticle concentration. Nanoparticles revealed physical stability against forces generated during aerosolization, what is attributed to the adsorbed PVA layer around the nanoparticles. Sildenafil was successfully encapsulated into nanoparticles (encapsulation efficiency: ∼80%). Size, size distribution and sildenafil content of nanoparticles were not affected by nebulization and the in vitro drug release profile demonstrated a sustained sildenafil release over ∼120 min. The current study suggests that the prepared sildenafil-loaded nanoparticles are a promising pharmaceutical for the therapy of pulmonary arterial hypertension.
authors: Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität Giessen, Klinikstrasse 36, D-35392 Giessen, Germany. moritz.beck-broichsitter@innere.med.uni-giessen.de
authors: Moritz
authors: M
authors: Beck-Broichsitter
authors: Pia
authors: P
authors: Kleimann
authors: Tobias
authors: T
authors: Gessler
authors: Werner
authors: W
authors: Seeger
authors: Thomas
authors: T
authors: Kissel
authors: Thomas
authors: T
authors: Schmehl
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles; D036103:Nanotechnology; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D010879:Piperazines / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011687:Purines / Q000008:administration & dosage / Q000737:chemistry; D000068677:Sildenafil Citrate; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013450:Sulfones / Q000008:administration & dosage* / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000737:chemistry; D014783:Viscosity
chemical_list: D000336:Aerosols; D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D012997:Solvents; D013450:Sulfones; D014665:Vasodilator Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011142:Polyvinyl Alcohol; D000068677:Sildenafil Citrate