Formulation development of freeze-dried oligonucleotide-loaded gelatin nanoparticles.
The freeze-drying properties of gelatin nanoparticles were investigated with the goal of providing practicable nanoparticle formulations for in vitro applications or clinical studies. Various excipients and rehydration protocols were assessed, and gelatin nanoparticles loaded with oligonucleotides were successfully freeze-dried and rehydrated. An NF-kappaB decoy oligonucleotide-loaded gelatin nanoparticle formulation was developed and applied in a drug targeting approach in an animal model. The high concentrations of nanoparticles achieved after rehydration with reduced volumes proved to be critical for the in vivo effect. Finally, short term storage stability under accelerated conditions was assessed for dried gelatin nanoparticles formulated in sucrose, trehalose, mannitol, or a mannitol/sucrose mixture. Size, size distribution, and residual moisture content were investigated. Sucrose- and trehalose-containing formulations exhibited the greatest stability, but mannitol-containing formulations also showed notable stabilization despite their crystalline nature.
Zillies
Jan C
JC
Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University Munich, Munich, Germany.
Zwiorek
Klaus
K
Hoffmann
Florian
F
Vollmar
Angelika
A
Anchordoquy
Thomas J
TJ
Winter
Gerhard
G
Coester
Conrad
C
D000818:Animals; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D005612:Freeze Drying; D005780:Gelatin / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D009841:Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013535:Suspensions
D008070:Lipopolysaccharides; D016328:NF-kappa B; D009841:Oligonucleotides; D013535:Suspensions; D005780:Gelatin