Co-delivery of dual toll-like receptor agonists and antigen in Poly(Lactic-Co-Glycolic) acid/polyethylenimine cationic hybrid nanoparticles promote efficient in vivo immune responses

Ebrahimian, M. and Hashemi, M. and Maleki, M. and Hashemitabar, G. and Abnous, K. and Ramezani, M. and Haghparast, A. (2017) Co-delivery of dual toll-like receptor agonists and antigen in Poly(Lactic-Co-Glycolic) acid/polyethylenimine cationic hybrid nanoparticles promote efficient in vivo immune responses. Frontiers in Immunology, 8 (SEP).

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Strategies to design delivery vehicles are critical in modern vaccine-adjuvant development. Nanoparticles (NPs) encapsulating antigen(s) and adjuvant(s) are promising vehicles to deliver antigen(s) and adjuvant(s) to antigen-presenting cells (APCs), allowing optimal immune responses against a specific pathogen. In this study, we developed a novel adjuvant delivery approach for induction of efficient in vivo immune responses. Polyethylenimine (PEI) was physically conjugated to poly(lactic-co-glycolic) acid (PLGA) to form PLGA/PEI NPs. This complex was encapsulated with resiquimod (R848) as toll-like receptor (TLR) 7/8 agonist, or monophosphoryl lipid A (MPLA) as TLR4 agonist and co-assembled with cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG ODN) as TLR9 agonist to form a tripartite formulation two TLR agonists (inside and outside NPs) and PLGA/PEI NPs as delivery system. The physicochemical characteristics, cytotoxicity and cellular uptake of these synthesized delivery vehicles were investigated. Cellular viability test revealed no pronounced cytotoxicity as well as increased cellular uptake compared to control groups in murine macrophage cells (J774 cell line). In the next step, PLGA (MPLA or R848)/PEI (CpG ODN) were co-delivered with ovalbumin (OVA) encapsulated into PLGA NPs to enhance the induction of immune responses. The immunogenicity properties of these co-delivery formulations were examined in vivo by evaluating the cytokine (IFN-γ, IL-4, and IL-1β) secretion and antibody (IgG1, IgG2a) production. Robust and efficient immune responses were achieved after in vivo administration of PLGA (MPLA or R848)/PEI (CpG ODN) co-delivered with OVA encapsulated in PLGA NPs in BALB/c mice. Our results demonstrate a rational design of using dual TLR agonists in a context-dependent manner for efficient nanoparticulate adjuvant-vaccine development. © 2017 Ebrahimian, Hashemi, Maleki, Hashemitabar, Abnous, Ramezani and Haghparast.

Item Type: Article
Additional Information: Cited By :14 Export Date: 16 February 2020 Correspondence Address: Haghparast, A.; Division of Biotechnology, Faculty of Veterinary Medicine, Ferdowsi University of MashhadIran; email:
Uncontrolled Keywords: Adjuvants CpG ODN Monophosphoryl lipid A Poly(lactic-co-glycolic) acid nanoparticles Polyethylenimine Resiquimod Toll-like receptor agonist Vaccine CpG oligodeoxynucleotide gamma interferon imidazoquinoline derivative immunoglobulin G1 immunoglobulin G2a interleukin 1beta interleukin 4 ovalbumin phosphoryl lipid A poly(lactic co glycolic) acid nanoparticle polyethyleneimine toll like receptor 4 toll like receptor 9 toll like receptor agonist unclassified drug agarose gel retardation assay animal cell animal experiment animal tissue antibody titer Article cell culture controlled study cytotoxicity drug analysis drug delivery system drug formulation drug release drug stability drug uptake encapsulation efficiency enzyme linked immunosorbent assay enzyme linked immunospot assay female flow cytometry gel electrophoresis immune response mouse MTT assay nonhuman particle size physical chemistry zeta potential
Subjects: QU Biochemistry
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib3 lib3
Date Deposited: 19 May 2020 07:31
Last Modified: 19 May 2020 07:31

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