Pulmonary drug delivery with aerosolizable nanoparticles in an ex vivo lung model.
The use of colloidal carrier systems for pulmonary drug delivery is an emerging field of interest in nanomedicine. The objective of this study was to compare the pulmonary absorption and distribution characteristics of the hydrophilic model drug 5(6)-carboxyfluorescein (CF) after aerosolization as solution or entrapped into nanoparticles in an isolated rabbit lung model (IPL). CF-nanoparticles were prepared from a new class of biocompatible, fast degrading, branched polyesters by a modified solvent displacement method. Physicochemical properties, morphology, encapsulation efficiency, in vitro drug release, stability of nanoparticles to nebulization, aerosol characteristics as well as pulmonary dye absorption and distribution profiles after nebulization in an IPL were investigated. CF-nanoparticles were spherical in shape with a mean particle size of 195.3+/-7.1nm, a polydispersity index of 0.225+/-0.017 and a zeta-potential of -28.3+/-0.3mV. Encapsulation efficiencies of CF were as high as about 60% (drug loading of 3% (w/w)); 90% of the entrapped CF were released during the first 50min in vitro. Nanoparticle characteristics were not significantly affected by the aerosolization process utilizing a vibrating mesh nebulizer. After deposition of equal amounts of CF in the IPL, less CF was detected in the perfusate for CF-nanoparticles (plateau concentration 9.2+/-2.4ng/ml) when compared to CF aerosolized from solution (17.7+/-0.8ng/ml). In conclusion, the data suggest that inhalative delivery of biodegradable nanoparticles may be a viable approach for pulmonary drug delivery. Moreover, a targeting effect to the lung tissue is claimed.
Department of Pharmaceutics and Biopharmacy, Philipps-University, Ketzerbach 63, D-35037 Marburg, Germany.
Moritz
M
Beck-Broichsitter
Julia
J
Gauss
Claudia B
CB
Packhaeuser
Kerstin
K
Lahnstein
Thomas
T
Schmehl
Werner
W
Seeger
Thomas
T
Kissel
Tobias
T
Gessler
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D005452:Fluoresceins / Q000008:administration & dosage / Q000737:chemistry; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D008954:Models, Biological; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D011817:Rabbits; D012995:Solubility; D013499:Surface Properties
D000336:Aerosols; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005452:Fluoresceins; D011091:Polyesters; D011145:Polyvinyls; C024098:6-carboxyfluorescein