title: Towards an inhalative in vivo application of immunomodulating gelatin nanoparticles in horse-related preformulation studies.
abstract: Delivering active ingredients using biocompatible and biodegradable carriers such as gelatin nanoparticles (GNPs) to the lung constitutes a promising non-invasive route of administration. However, the pulmonary delivery of nanoparticle-based immunotherapy is still a field that requires more clarification.   In this study, GNPs loaded with cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODN)-loaded and plain GNPs were aerosolised either by a conventional pressured metered dose inhaler (pMDI) or by active or passive vibrating-mesh (VM) nebulisers. GNP sizes after nebulisation by active and passive VM nebulisers were 248.2 ± 7.34 and 222.3 ± 1.42 nm, respectively. GNP concentrations after aerosolisation were found consistent and second-stage particle deposition in an impinger was up to 65.68 ± 11.2% of the nebulised dose. VM nebulisers produced high fine particle fractions, while pMDIs did not. Nebulised CpG-ODN-loaded GNPs remained capable to stimulate IL-10 release (225.2 ± 56.3 pg/ml) in vitro from equine alveolar lymphocytes. Thus, a novel system for pulmonary GNP-mediated immunotherapy in vivo was established.
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology and Biopharmacy, Ludwig Maximilians University, Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fuchs
authors.forename: John
authors.initials: J
authors.lastname: Klier
authors.forename: Anna
authors.initials: A
authors.lastname: May
authors.forename: Gerhard
authors.initials: G
authors.lastname: Winter
authors.forename: Conrad
authors.initials: C
authors.lastname: Coester
authors.forename: Heidrun
authors.initials: H
authors.lastname: Gehlen
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D005780:Gelatin / Q000737:chemistry / Q000494:pharmacology*; D006736:Horses; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D053758:Nanoparticles; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000378:metabolism
chemical_list: C408982:CPG-oligonucleotide; D007155:Immunologic Factors; D009838:Oligodeoxyribonucleotides; D016753:Interleukin-10; D005780:Gelatin