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Cited by 59Advanced Drug Delivery SystemsImmunotherapy and Immune ResponsesNanoparticle-Based Drug Delivery

Biodegradable microspheres alone do not stimulate murine macrophages in vitro, but prolong antigen presentation by macrophages in vitro and stimulate a solid immune response in mice

Luzardo-Alvarez, Asteria, Blarer, Natalia, Peter, Katrin, Romero, Jackeline F., Reymond, Christophe, Corradin, Giampietro, Gander, Bruno·2005·Journal of Controlled Release
DOI 10.1016/j.jconrel.2005.09.015
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Abstract

The purpose of this study was to analyze the potential of various types of biodegradable microspheres (MS) (i) to activate in vitro cell line-derived macrophages (RAW 264.7, Mphi), and primary peritoneal and bone marrow-derived mouse Mphi, to prolong the release and presentation of microencapsulated synthetic malaria antigens by Mphi after uptake of antigen-loaded MS, and (ii) to stimulate an immune response in mice against a microencapsulated synthetic malaria antigen. The MS were made of various types of poly(lactide-co-glycolide) (PLGA) or chitosan cross-linked with tripolyphosphate. PLGA, but not chitosan MS, were efficiently ingested by Mphi. Upon exposure to the various MS types, Mphi increased only the production of reactive oxygen intermediates (ROI), while the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), and the expression of cyclooxigenase-2 (COX-2), inducible NO synthase (iNOS), the cell surface markers MHC class I and II, and CD 86 remained unaffected. In vitro release of the microencapsulated antigen from PLGA50:50 MS followed a pulsatile pattern and extended over 14 weeks. This prolonged antigen release was also mirrored in the significantly prolonged antigen presentation over more than 7 days by Mphi after uptake of antigen-loaded PLGA MS. Finally, antigen-loaded PLGA MS induced a solid immune response in mice after a single s.c.-injection, which was only slightly inferior to the antibody titers measured with the control formulation with Montanide ISA720. These results suggest that MS are well tolerated by Mphi. The prolonged antigen presentation by Mphi, as measured in vitro, along with the capacity to induce a strong immune response in animals emphasize that biodegradable MS are a very promising delivery system for both preventive and immunotherapeutic vaccines.

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Crossref · 10.1016/j.jconrel.2005.09.015

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  • Particle structures smaller than 5 μm are taken up by APCs such as dendritic cells and macrophages and transported directly to the lymph node, where encapsulated antigen can be presented to T cells.

    “Particle structures smaller than 5 μm are taken up by APCs, such as dendritic cells (DCs) and macrophages [59–61], and are transported directly to the lymph node [58], where the encapsulated antigen can be presented to T cells.”

    From Use of lectin-functionalized particles for oral immunotherapy (2012) · cites this paper as [61]

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Authors
Luzardo-Alvarez, A., Blarer, N., Peter, K., Romero, J. F., Reymond, C., Corradin, G., & Gander, B.
Affiliations
  • ETH Zurich (CH)
  • University of Lausanne (CH)
Corresponding author
Gander, Bruno
ORCID
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2005-12
Volume
109
Issue
1-3
Pages
62-76
ISSN
0168-3659 (ISSN-L)
DOI
10.1016/j.jconrel.2005.09.015
OpenAlex
W1994046518
Cited by
59
References
53
Citations by year
2025: 1 · 2023: 1 · 2020: 2 · 2019: 4 · 2017: 5 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 4
FWCI
3.99
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Journal of Controlled Release (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
Funders
Kommission für Technologie und Innovation
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
biodegradable microspheres, macrophage activation, antigen presentation, PLGA microspheres, chitosan microspheres, malaria vaccine, controlled antigen release, reactive oxygen species, nitric oxide, cyclooxygenase-2, MHC class I and II expression, CD86, vaccine delivery systems, immunotherapy
MeSH terms
Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Antigens, Protozoan, Cells, Cultured, Drug Compounding, Enzyme-Linked Immunosorbent Assay, Genes, MHC Class II, Genes, MHC Class I, Macrophages, Mice, Inbred BALB C, Microspheres, Nitric Oxide, Phagocytosis, Plasmodium falciparum, Polyglycolic Acid, Polymers, Spectrometry, Fluorescence, Tumor Necrosis Factor-alpha, Respiratory Burst, Antigen Presentation, Lactic Acid, Mice, Cyclooxygenase 2, Nitric Oxide Synthase Type II, In Vitro Techniques

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