Towards an inhalative in vivo application of immunomodulating gelatin nanoparticles in horse-related preformulation studies

• Published in: Journal of microencapsulation Vol. 29; no. 7; pp. 615 - 625
• Main Authors: Fuchs, Sebastian, Klier, John, May, Anna, Winter, Gerhard, Coester, Conrad, Gehlen, Heidrun
• Format: Journal Article
• Language: English
• Published: England Informa UK, Ltd 01-11-2012; Taylor & Francis
• Subjects: Administration, Inhalation; aerosol; Animals; gelatin; Gelatin - chemistry; Gelatin - pharmacology; Horses; Immunologic Factors - chemistry; Immunologic Factors - pharmacology; immunology; Immunotherapy - methods; Interleukin-10 - metabolism; Male; nanoparticle; Nanoparticles; Oligodeoxyribonucleotides - chemistry; Oligodeoxyribonucleotides - pharmacology; oligonucleotides; Pulmonary Alveoli - metabolism; pulmonary drug delivery
• ISSN: 0265-2048; 1464-5246
• DOI: 10.3109/02652048.2012.668962

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.