Induction of a balanced Th1/Th2 immune responses by co-delivery of PLGA/ovalbumin nanospheres and CpG ODNs/PEI-SWCNT nanoparticles as TLR9 agonist in BALB/c mice
| Autor: | Mahboubeh Ebrahimian, Gholamreza Hashemitabar, Mohsen Maleki, Mohammad Ramezani, Maryam Hashemi, Khalil Abnous, Alireza Haghparast |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
CpG Oligodeoxynucleotide Ovalbumin medicine.medical_treatment Pharmaceutical Science Antigen-Presenting Cells 02 engineering and technology Pharmacology Cell Line 03 medical and health sciences chemistry.chemical_compound Mice Th2 Cells Antigen Adjuvants Immunologic Polylactic Acid-Polyglycolic Acid Copolymer medicine Animals Polyethyleneimine Lactic Acid Cytotoxicity Polyethylenimine Mice Inbred BALB C biology Chemistry Nanotubes Carbon Macrophages technology industry and agriculture TLR9 Th1 Cells 021001 nanoscience & nanotechnology Molecular biology PLGA 030104 developmental biology Oligodeoxyribonucleotides Toll-Like Receptor 9 biology.protein Female 0210 nano-technology Adjuvant Nanospheres Polyglycolic Acid |
| Zdroj: | International journal of pharmaceutics. 515(1-2) |
| ISSN: | 1873-3476 |
| Popis: | To develop effective and safe vaccines with reduced dose of antigen and adjuvant, intelligent delivery systems are required. Many delivery systems have been developed to enhance the biological activity of cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG ODN) as both immunotherapeutic agents and vaccine adjuvants. In this study we designed a novel CpG ODN delivery system based on single-walled carbon nanotube (SWCNT) functionalized with polyethylenimine (PEI) and alkylcarboxylated PEI (AL-PEI). The physicochemical characteristics, cytotoxicity and cellular uptake studies of these carriers were performed. All carriers were conjugated with CpG ODN followed by co-delivery with ovalbumin (OVA) encapsulated into poly (lactic-co-glycolic acid) nanospheres (PLGA NSs) to enhance the induction of immune responses. The effect of these formulations on antibody (IgG1, IgG2a) and cytokine (IL-1β, IFN-γ, IL-4) production was evaluated in an in vivo experiment. The results showed that all nano-adjuvant formulations had a strong influence in up-regulation of IFN-γ and IL-4 in parallel with high IgG1-IgG2a isotype antibody titers in mice. In particular, SWCNT-AL-PEI nano-adjuvant formulation generated a balanced Th1 and Th2 immune response with more biased toward Th1 response without exhibiting any inflammatory and toxic effects. Therefore this nano-adjuvant formulation could be used as an efficient prophylactic immune responses agent. |
| Databáze: | OpenAIRE |
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