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A nebulized gelatin nanoparticle-based CpG formulation is effective in immunotherapy of allergic horses.
Abstract: In the recent years, nanotechnology has boosted the development of potential drug delivery systems and material engineering on nanoscale basis in order to increase drug specificity and reduce side effects. A potential delivery system for immunostimulating agents such as cytosine-phosphate-guanine-oligodeoxynucleotides (CpG-ODN) needs to be developed to maximize the efficacy of immunotherapy against hypersensitivity. In this study, an aerosol formulation of biodegradable, biocompatible and nontoxic gelatin nanoparticle-bound CpG-ODN 2216 was used to treat equine recurrent airway obstruction in a clinical study. Methods: Bronchoalveolar lavage fluid was obtained from healthy and allergic horses to quantify Th1/Th2 cytokine levels before and after inhalation regimen. Full clinical examinations were performed to evaluate the therapeutic potential of this nebulized gelatin nanoparticle-based CpG formulation. Results: Most remarkable was that regulatory anti-inflammatory and anti-allergic cytokine IL-10 expression was significantly triggered by five consecutive inhalations. Thorough assessment of clinical parameters following nanoparticle treatment indicated a partial remission of the allergic condition. Conclusions: Thus this study, for the first time, showed effectiveness of colloidal nanocarrier-mediated immunotherapy in food-producing animals with potential future applicability to other species including humans.
Publication Date: 2012-02-04 PubMed ID: 22302522DOI: 10.1007/s11095-012-0686-8Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study describes how nanotechnology is used to formulate a sprayable immunotherapy medication for horses suffering from recurrent airway obstruction. It shows that this treatment methodology is effective in managing allergy symptoms in the tested animals.
Introduction and Study Background
- The researchers centered their study around nanotechnology, an innovative field that’s expediting the development of new drug delivery systems intended to enhance drug precision and lessen side effects.
- The focus was to establish an optimum delivery system for immunostimulating agents such as cytosine-phosphate-guanine-oligodeoxynucleotides (CpG-ODN), with the aim of boosting the effectiveness of immunotherapy in combatting hypersensitivity.
Methodology
- In the study, an aerosol formulation of biodegradable, biocompatible, and non-toxic gelatin nanoparticle-bound CpG-ODN 2216 was used to treat equine recurrent airway obstruction.
- Samples of Bronchoalveolar lavage fluid were collected from both healthy and allergic horses to measure Th1/Th2 cytokine levels before and after administering the inhalation treatment.
- Comprehensive clinical examinations were also carried out to determine the therapeutic effectiveness of the nebulized gelatin nanoparticle-based CpG formulation.
Key Findings
- The most notable finding was that the expression of the regulatory anti-inflammatory and anti-allergic cytokine known as IL-10 was significantly activated after five consecutive inhalations.
- Close evaluation of clinical parameters following the nanoparticle treatment pointed to a partial remission of the symptoms linked to allergies.
Implications and Conclusion
- This research is groundbreaking, as it demonstrated for the first time the effectiveness of a colloidal nanocarrier-mediated immunotherapy approach in food-producing animals.
- It posits that this treatment methodology has the potential to be applied to other species, including humans, in the future.
Cite This Article
APA
Klier J, Fuchs S, May A, Schillinger U, Plank C, Winter G, Coester C, Gehlen H.
(2012).
A nebulized gelatin nanoparticle-based CpG formulation is effective in immunotherapy of allergic horses.
Pharm Res, 29(6), 1650-1657.
https://doi.org/10.1007/s11095-012-0686-8 Publication
Researcher Affiliations
- Department of Veterinary Medicine, Equine Clinic, Ludwig Maximilians University, Munich, Germany.
MeSH Terms
- Adjuvants, Immunologic / administration & dosage
- Adjuvants, Immunologic / chemistry
- Administration, Inhalation
- Aerosols
- Airway Obstruction / immunology
- Airway Obstruction / therapy
- Airway Obstruction / veterinary
- Animals
- Bronchoalveolar Lavage Fluid / immunology
- Cells, Cultured
- Chemistry, Pharmaceutical
- Cytokines / metabolism
- Drug Administration Schedule
- Drug Carriers
- Gelatin / chemistry
- Horse Diseases / immunology
- Horse Diseases / therapy
- Horses
- Immunotherapy / veterinary
- Nanoparticles
- Nanotechnology
- Nebulizers and Vaporizers
- Oligodeoxyribonucleotides / administration & dosage
- Oligodeoxyribonucleotides / chemistry
- Recurrence
- Respiratory Hypersensitivity / immunology
- Respiratory Hypersensitivity / therapy
- Respiratory Hypersensitivity / veterinary
- Technology, Pharmaceutical / methods
- Th1 Cells / immunology
- Th2 Cells / immunology
- Toll-Like Receptor 9 / agonists
References
This article includes 29 references
- von Garnier C, Nicod LP. Immunology taught by lung dendritic cells.. Swiss Med Wkly 2009 Apr 4;139(13-14):186-92.
- Krieg AM. CpG motifs in bacterial DNA and their immune effects.. Annu Rev Immunol 2002;20:709-60.
- Xiao K, Luo J, Fowler WL, Li Y, Lee JS, Xing L, Cheng RH, Wang L, Lam KS. A self-assembling nanoparticle for paclitaxel delivery in ovarian cancer.. Biomaterials 2009 Oct;30(30):6006-16.
- Lewkowicz P, Lewkowicz N, Sasiak A, Tchu00f3rzewski H. Lipopolysaccharide-activated CD4+CD25+ T regulatory cells inhibit neutrophil function and promote their apoptosis and death.. J Immunol 2006 Nov 15;177(10):7155-63.
- Moseman EA, Liang X, Dawson AJ, Panoskaltsis-Mortari A, Krieg AM, Liu YJ, Blazar BR, Chen W. Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells.. J Immunol 2004 Oct 1;173(7):4433-42.
- Zhou Q, Sun X, Zeng L, Liu J, Zhang Z. A randomized multicenter phase II clinical trial of mitoxantrone-loaded nanoparticles in the treatment of 108 patients with unresected hepatocellular carcinoma.. Nanomedicine 2009 Dec;5(4):419-23.
- Vollmer J, Krieg AM. Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists.. Adv Drug Deliv Rev 2009 Mar 28;61(3):195-204.
- Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J. Regulatory T cells selectively express toll-like receptors and are activated by lipopolysaccharide.. J Exp Med 2003 Feb 17;197(4):403-11.
- Bourquin C, Wurzenberger C, Heidegger S, Fuchs S, Anz D, Weigel S, Sandholzer N, Winter G, Coester C, Endres S. Delivery of immunostimulatory RNA oligonucleotides by gelatin nanoparticles triggers an efficient antitumoral response.. J Immunother 2010 Nov-Dec;33(9):935-44.
- Moreno-Aspitia A, Perez EA. Nanoparticle albumin-bound paclitaxel (ABI-007): a newer taxane alternative in breast cancer.. Future Oncol 2005 Dec;1(6):755-62.
- Bourquin C, Anz D, Zwiorek K, Lanz AL, Fuchs S, Weigel S, Wurzenberger C, von der Borch P, Golic M, Moder S, Winter G, Coester C, Endres S. Targeting CpG oligonucleotides to the lymph node by nanoparticles elicits efficient antitumoral immunity.. J Immunol 2008 Sep 1;181(5):2990-8.
- Jarnicki AG, Conroy H, Brereton C, Donnelly G, Toomey D, Walsh K, Sweeney C, Leavy O, Fletcher J, Lavelle EC, Dunne P, Mills KH. Attenuating regulatory T cell induction by TLR agonists through inhibition of p38 MAPK signaling in dendritic cells enhances their efficacy as vaccine adjuvants and cancer immunotherapeutics.. J Immunol 2008 Mar 15;180(6):3797-806.
- Stock P, Akbari O, Berry G, Freeman GJ, Dekruyff RH, Umetsu DT. Induction of T helper type 1-like regulatory cells that express Foxp3 and protect against airway hyper-reactivity.. Nat Immunol 2004 Nov;5(11):1149-56.
- Lavoie JP, Maghni K, Desnoyers M, Taha R, Martin JG, Hamid QA. Neutrophilic airway inflammation in horses with heaves is characterized by a Th2-type cytokine profile.. Am J Respir Crit Care Med 2001 Oct 15;164(8 Pt 1):1410-3.
- Gerber V, Straub R, Marti E, Hauptman J, Herholz C, King M, Imhof A, Tahon L, Robinson NE. Endoscopic scoring of mucus quantity and quality: observer and horse variance and relationship to inflammation, mucus viscoelasticity and volume.. Equine Vet J 2004 Nov;36(7):576-82.
- Hartl D, Koller B, Mehlhorn AT, Reinhardt D, Nicolai T, Schendel DJ, Griese M, Krauss-Etschmann S. Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthma.. J Allergy Clin Immunol 2007 May;119(5):1258-66.
- Umetsu DT, DeKruyff RH. The regulation of allergy and asthma.. Immunol Rev 2006 Aug;212:238-55.
- Zwiorek K, Bourquin C, Battiany J, Winter G, Endres S, Hartmann G, Coester C. Delivery by cationic gelatin nanoparticles strongly increases the immunostimulatory effects of CpG oligonucleotides.. Pharm Res 2008 Mar;25(3):551-62.
- Ryanna K, Stratigou V, Safinia N, Hawrylowicz C. Regulatory T cells in bronchial asthma.. Allergy 2009 Mar;64(3):335-47.
- Coester CJ, Langer K, van Briesen H, Kreuter J. Gelatin nanoparticles by two step desolvation--a new preparation method, surface modifications and cell uptake.. J Microencapsul 2000 Mar-Apr;17(2):187-93.
- Klier J, May A, Fuchs S, Schillinger U, Plank C, Winter G, Gehlen H, Coester C. Immunostimulation of bronchoalveolar lavage cells from recurrent airway obstruction-affected horses by different CpG-classes bound to gelatin nanoparticles.. Vet Immunol Immunopathol 2011 Nov 15;144(1-2):79-87.
- Gerber V, Baleri D, Klukowska-Ru00f6tzler J, Swinburne JE, Dolf G. Mixed inheritance of equine recurrent airway obstruction.. J Vet Intern Med 2009 May-Jun;23(3):626-30.
- Taylor A, Verhagen J, Blaser K, Akdis M, Akdis CA. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells.. Immunology 2006 Apr;117(4):433-42.
- Montagnoli C, Fallarino F, Gaziano R, Bozza S, Bellocchio S, Zelante T, Kurup WP, Pitzurra L, Puccetti P, Romani L. Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolism.. J Immunol 2006 Feb 1;176(3):1712-23.
- Bohle B. CpG motifs as possible adjuvants for the treatment of allergic diseases.. Int Arch Allergy Immunol 2002 Nov;129(3):198-203.
- Jurk M, Vollmer J. Therapeutic applications of synthetic CpG oligodeoxynucleotides as TLR9 agonists for immune modulation.. BioDrugs 2007;21(6):387-401.
- van Scott MR, Justice JP, Bradfield JF, Enright E, Sigounas A, Sur S. IL-10 reduces Th2 cytokine production and eosinophilia but augments airway reactivity in allergic mice.. Am J Physiol Lung Cell Mol Physiol 2000 Apr;278(4):L667-74.
- Kline JN. Immunotherapy of asthma using CpG oligodeoxynucleotides.. Immunol Res 2007;39(1-3):279-86.
- Senti G, Johansen P, Haug S, Bull C, Gottschaller C, Mu00fcller P, Pfister T, Maurer P, Bachmann MF, Graf N, Ku00fcndig TM. Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial.. Clin Exp Allergy 2009 Apr;39(4):562-70.
Citations
This article has been cited 11 times.- Klier J, Fuchs S, Winter G, Gehlen H. Inhalative Nanoparticulate CpG Immunotherapy in Severe Equine Asthma: An Innovative Therapeutic Concept and Potential Animal Model for Human Asthma Treatment.. Animals (Basel) 2022 Aug 16;12(16).
- Reddy PRK, Yasaswini D, Reddy PPR, Zeineldin M, Adegbeye MJ, Hyder I. Applications, challenges, and strategies in the use of nanoparticles as feed additives in equine nutrition.. Vet World 2020 Aug;13(8):1685-1696.
- Pali-Schu00f6ll I, DeBoer DJ, Alessandri C, Seida AA, Mueller RS, Jensen-Jarolim E. Formulations for Allergen Immunotherapy in Human and Veterinary Patients: New Candidates on the Horizon.. Front Immunol 2020;11:1697.
- Hue E, Orard M, Toquet MP, Depecker M, Couroucu00e9 A, Pronost S, Paillot R, Richard EA. Asymmetrical Pulmonary Cytokine Profiles Are Linked to Bronchoalveolar Lavage Fluid Cytology of Horses With Mild Airway Neutrophilia.. Front Vet Sci 2020;7:226.
- Youssef FS, El-Banna HA, Elzorba HY, Galal AM. Application of some nanoparticles in the field of veterinary medicine.. Int J Vet Sci Med 2019;7(1):78-93.
- Barton AK, Shety T, Klier J, Geis S, Einspanier R, Gehlen H. Metalloproteinases and their Inhibitors under the Course of Immunostimulation by CPG-ODN and Specific Antigen Inhalation in Equine Asthma.. Mediators Inflamm 2019;2019:7845623.
- Klier J, Bartl C, Geuder S, Geh KJ, Reese S, Goehring LS, Winter G, Gehlen H. Immunomodulatory asthma therapy in the equine animal model: A dose-response study and evaluation of a long-term effect.. Immun Inflamm Dis 2019 Sep;7(3):130-149.
- Klier J, Geis S, Steuer J, Geh K, Reese S, Fuchs S, Mueller RS, Winter G, Gehlen H. A comparison of nanoparticullate CpG immunotherapy with and without allergens in spontaneously equine asthma-affected horses, an animal model.. Immun Inflamm Dis 2018 Mar;6(1):81-96.
- Yin L, Yuvienco C, Montclare JK. Protein based therapeutic delivery agents: Contemporary developments and challenges.. Biomaterials 2017 Jul;134:91-116.
- Barton AK, Gehlen H. Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?. Mediators Inflamm 2016;2016:5693205.
- Klier J, Lehmann B, Fuchs S, Reese S, Hirschmann A, Coester C, Winter G, Gehlen H. Nanoparticulate CpG immunotherapy in RAO-affected horses: phase I and IIa study.. J Vet Intern Med 2015 Jan;29(1):286-93.
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