Stabilization of aerosolizable nano-carriers by freeze-drying.
OBJECTIVE
This study investigates the feasibility of freeze-drying aerosolizable nano-carriers (NC) by the use of different lyoprotective agents (LPA) and the influence of the freeze-drying on the physicochemical properties of these nano-carriers and on their aerosolization.


METHODS
Nano-carriers were prepared from fast-degrading polymers, DMAPA(24)-PVAL-g-PLGA(1:7.5) and DEAPA(26)-PVAL-g-PLGA(1:10), and freeze-dried using increasing concentrations of different LPA. The hydrodynamic diameter, zeta potential and morphology (atomic force microscopy) of NC were characterized before and after freeze-drying. The ability to aerosolize using a jet nebulizer and an electronic micro-pump nebulizer was also investigated.


RESULTS
Freeze-drying with LPA led to a decreased zeta-potential of NC and changes in size about 20 nm without alteration in shape, whereas lyophilizates without LPA were found to aggregate. While freeze-drying was positively affected by increasing concentrations, it was not influenced by the type of LPA. The possibility for aerosolization was not influenced by any LPA.


CONCLUSIONS
Freeze-drying with LPA is a suitable method to physically stabilize fast-degrading NC from aqueous suspensions without influencing the aerosolizability.
Department of Pharmaceutics and Biopharmacy, Philipps-University, Ketzerbach 63, 35032, Marburg, Germany.
Claudia B
CB
Packhaeuser
Kerstin
K
Lahnstein
Johannes
J
Sitterberg
Thomas
T
Schmehl
Tobias
T
Gessler
Udo
U
Bakowsky
Werner
W
Seeger
Thomas
T
Kissel
D000336:Aerosols; D001152:Arsenicals; D004337:Drug Carriers / Q000737:chemistry*; D004563:Electrochemistry; D005079:Excipients; D005612:Freeze Drying; D019344:Lactic Acid; D017078:Laser-Doppler Flowmetry; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry*; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011098:Polyglactin 910 / Q000031:analogs & derivatives; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D011142:Polyvinyl Alcohol; D013535:Suspensions; D014783:Viscosity
D000336:Aerosols; D001152:Arsenicals; D004337:Drug Carriers; D005079:Excipients; D011108:Polymers; D013535:Suspensions; C483759:diethylaminopropyl amine-poly(vinyl alcohol)-grafted-poly(lactide-co-glycolide); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011098:Polyglactin 910; C044974:dimethylarsinopenicillamine; D011142:Polyvinyl Alcohol