title: Formulation development of freeze-dried oligonucleotide-loaded gelatin nanoparticles.
abstract: 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.
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Zillies
authors.forename: Klaus
authors.initials: K
authors.lastname: Zwiorek
authors.forename: Florian
authors.initials: F
authors.lastname: Hoffmann
authors.forename: Angelika
authors.initials: A
authors.lastname: Vollmar
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Anchordoquy
authors.forename: Gerhard
authors.initials: G
authors.lastname: Winter
authors.forename: Conrad
authors.initials: C
authors.lastname: Coester
mesh_terms: 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
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D009841:Oligonucleotides; D013535:Suspensions; D005780:Gelatin