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Journal of microencapsulation2012; 29(7); 615-625; doi: 10.3109/02652048.2012.668962

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.
Publication Date: 2012-03-20 PubMed ID: 22432849DOI: 10.3109/02652048.2012.668962Google Scholar: Lookup
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  • Journal Article

Summary

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The study presents a novel system for the pulmonary application of immunotherapy in horses using gelatin nanoparticles (GNPs) loaded with immunomodulating agents, delivered through different types of nebulisers.

Introduction and Objectives

  • The researchers focused on studying the potential of a non-invasive route of delivering active ingredients through the lungs using biocompatible and biodegradable carriers like gelatin nanoparticles (GNPs).
  • A key aspect of the study was to understand and further examine the field of nanoparticle-based immunotherapy.
  • The goal was to develop a novel system for administering immunotherapy in horses via their lungs using GNPs.

Methods

  • Gelatin nanoparticles (GNPs) were loaded with cytosine-phosphate-guanine oligodeoxynucleotides (CpG-ODN), a type of immunomodulator.
  • These CpG-ODN-loaded and plain GNPs were aerosolised using three different types of nebulisers, specifically a conventional pressured metered-dose inhaler (pMDI), and active or passive vibrating-mesh (VM) nebulisers.
  • The size and concentration of the GNPs post-aerosolisation, as well as the amount of second-stage particle deposition in an impinger, were all measured and recorded.

Results and Findings

  • The sizes of GNPs after aerosolisation with active and passive VM nebulisers were found to be 248.2 ± 7.34 and 222.3 ± 1.42 nm, respectively.
  • The concentrations of GNPs post-aerosolisation were consistent and a second-stage particle deposition in an impinger accounted for up to 65.68 ± 11.2% of the nebulised dose.
  • VM nebulisers were found to be more effective than pMDIs, producing higher fine particle fractions.
  • Nebulised CpG-ODN-loaded GNPs remained active, promoting the release of IL-10 (225.2 ± 56.3 pg/ml), a key anti-inflammatory cytokine, in the in-vitro sample from equine alveolar lymphocytes.

Conclusion

  • The study successfully established a novel system of in vivo pulmonary application of GNP-mediated immunotherapy in horses.
  • The results suggest the potential of VM nebulisers in effectively delivering nanoscale particle therapy for diseases that need immunological intervention.

Cite This Article

APA
Fuchs S, Klier J, May A, Winter G, Coester C, Gehlen H. (2012). Towards an inhalative in vivo application of immunomodulating gelatin nanoparticles in horse-related preformulation studies. J Microencapsul, 29(7), 615-625. https://doi.org/10.3109/02652048.2012.668962

Publication

ISSN: 1464-5246
NlmUniqueID: 8500513
Country: England
Language: English
Volume: 29
Issue: 7
Pages: 615-625

Researcher Affiliations

Fuchs, Sebastian
  • Department of Pharmacy, Pharmaceutical Technology and Biopharmacy, Ludwig Maximilians University, Munich, Germany.
Klier, John
    May, Anna
      Winter, Gerhard
        Coester, Conrad
          Gehlen, Heidrun

            MeSH Terms

            • Administration, Inhalation
            • Animals
            • Gelatin / chemistry
            • Gelatin / pharmacology
            • Horses
            • Immunologic Factors / chemistry
            • Immunologic Factors / pharmacology
            • Immunotherapy / methods
            • Interleukin-10 / metabolism
            • Male
            • Nanoparticles
            • Oligodeoxyribonucleotides / chemistry
            • Oligodeoxyribonucleotides / pharmacology
            • Pulmonary Alveoli / metabolism

            Citations

            This article has been cited 9 times.
            1. 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).
              doi: 10.3390/ani12162087pubmed: 36009677google scholar: lookup
            2. 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.
            3. 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.
              doi: 10.1155/2019/7845623pubmed: 31316303google scholar: lookup
            4. DeFrates K, Markiewicz T, Gallo P, Rack A, Weyhmiller A, Jarmusik B, Hu X. Protein Polymer-Based Nanoparticles: Fabrication and Medical Applications. Int J Mol Sci 2018 Jun 9;19(6).
              doi: 10.3390/ijms19061717pubmed: 29890756google scholar: lookup
            5. 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.
              doi: 10.1002/iid3.198pubmed: 29094511google scholar: lookup
            6. Yin L, Yuvienco C, Montclare JK. Protein based therapeutic delivery agents: Contemporary developments and challenges. Biomaterials 2017 Jul;134:91-116.
            7. 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.
              doi: 10.1111/jvim.12524pubmed: 25619520google scholar: lookup
            8. Kazemi M. Revolutionizing Veterinary Medicine: The Role of Nanoparticles in Advancing Animal Health, Nutrition and Disease Management. Vet Med Sci 2025 Sep;11(5):e70528.
              doi: 10.1002/vms3.70528pubmed: 40747873google scholar: lookup
            9. Wang Q, Bu C, Dai Q, Chen J, Zhang R, Zheng X, Ren H, Xin X, Li X. Recent Progress in Nucleic Acid Pulmonary Delivery toward Overcoming Physiological Barriers and Improving Transfection Efficiency. Adv Sci (Weinh) 2024 May;11(18):e2309748.
              doi: 10.1002/advs.202309748pubmed: 38460157google scholar: lookup