Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis

Gómez, Julia M. Martínez; Csaba, Nœmi; Fischer, Stefan; Sichelstiel, Anke; Kündig, Thomas M.; Gander, Bruno; Johansen, Pål

doi:10.1016/j.jconrel.2008.06.003

Cited by 58 publications

(26 citation statements)

References 47 publications

(23 reference statements)

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“…SEM images of these particles (Figure 1) show smooth surface morphology and confirm the size obtained from volume impedance measurements. The size distribution observed in the SEM images is characteristic of the microparticle synthesis procedure described above, and has been reported elsewhere [9, 23, 24]. Further, the zeta potential of these rapaMPs was determined to be -35.38 ± 4.49 mV (n=4 particle sets).…”

Section: Resultssupporting

confidence: 67%

Delivery of rapamycin to dendritic cells using degradable microparticles

Jhunjhunwala

Raimondi

Thomson

et al. 2009

Journal of Controlled Release

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Degradable microparticles have the potential to protect and release drugs over extended periods and, if sized appropriately, can be passively targeted to phagocytic cells in vivo. Dendritic cells (DC) are a class of phagocytic cells known to play important roles in transplant rejection. Previously, we have demonstrated that DC treated with an immunosuppressive drug, rapamycin, have the ability to suppress transplant rejection. Herein, we describe a strategy to deliver an intracellular depot of rapamycin to DC. To achieve this, rapamycin was encapsulated into ∼3.4 μm sized poly(lactic-co-glycolic)acid (PLGA) microparticles (rapaMPs), and release behavior was examined under intra-phagosomal (pH = 5) and extracellular (pH = 7.4) conditions. It was observed that 4 days following phagocytosis of rapaMP, DC have significantly reduced ability to activate T cells, in comparison to DC treated with soluble rapamycin. Hence, we conclude that DC-specific intracellular delivery of rapamycin results in better efficacy of the drug, with respect to its ability to modulate DC function, when compared to treating DC with extracellular rapamycin.

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Section: Resultssupporting

confidence: 67%

Delivery of rapamycin to dendritic cells using degradable microparticles

Jhunjhunwala

Raimondi

Thomson

et al. 2009

Journal of Controlled Release

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“…The polymer type, the surface decoration of the particles, as well as further excipients and adjuvants all represent factors that enable the modulation of the immunological properties of a particle-based Ag delivery system (35,(46)(47)(48)(49)(50)(51)(52). In studies in which PLGA microparticles were shown to stimulate APCs associated with the release of Ags into the cytosol as consequence of destabilization of the endosomal membrane (53)(54)(55).…”

Section: Discussionmentioning

confidence: 99%

Photosensitizer and Light Pave the Way for Cytosolic Targeting and Generation of Cytosolic CD8 T Cells Using PLGA Vaccine Particles

Bruno

Waeckerle-Men

Håkerud

et al. 2015

The Journal of Immunology

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The generation of CTLs is crucial in the immunological fight against cancer and many infectious diseases. To achieve this, vaccine Ags need to be targeted to the cytosol of dendritic cells, which can activate CD8 T cells via MHC class I (MHCI). Therefore, such targeting has become one of the major objectives of vaccine research. In this study, we aimed to bypass the unwanted and default MHC class II Ag presentation and trigger MHCI presentation by using a photosensitizer that, upon light activation, would facilitate cytosolic targeting of codelivered Ag. Poly(lactide-co-glycolide) microparticles ∼1 μm size were loaded with OVA and the photosensitizer tetraphenyl chlorine disulphonate (TPCS2a) and administered intradermally in mice, which were illuminated 1 d later for activation of the photosensitizer. Immunization in the presence of TPCS2a significantly increased activation of CD8 T cells compared with immunization without TPCS2a and as measured by CD8 T cell proliferation, production of proinflammatory IFN-γ, TNF-α, and IL-2, and prevention of tumor growth. Cytotoxicity was demonstrated by granzyme B production in vitro and by in vivo killing of CFSE-labeled targets. CD4-dependent Ab responses were abrogated in mice immunized with TPCS2a-containing particles, suggesting that photosensitization facilitated a shift from default MHC class II toward MHCI Ag presentation. Hence, vaccine particles with Ag and photosensitizers proved an effective vehicle or adjuvant for stimulation of CTLs, and they may find potential application in therapeutic cancer vaccination and in prophylactic and therapeutic vaccination against intracellular infections.

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“…37 Furthermore, coating PLGA MPs with protamine, an arginine-rich peptide with strong basic charge, resulted in increased antibodies and T-cell responses in mice. 116 In addition, cellular evidence for enhanced cross-presentation of exogenous antigens encapsulated in protamine-coated PLGA NPs through facilitated antigen uptake and lysosomal escape was provided. These results suggest that protamine-modified PLGA NPs maybe used as a potent adjuvant for cellular vaccines.…”

Section: Cationic Agentsmentioning

confidence: 99%

Peptide/protein vaccine delivery system based on PLGA particles

Allahyari

Mohit

2015

Human Vaccines & Immunotherapeutics

179

118

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Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DCbased vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to Mcells will be highlighted.

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Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis

Cited by 58 publications

References 47 publications

Delivery of rapamycin to dendritic cells using degradable microparticles

Delivery of rapamycin to dendritic cells using degradable microparticles

Photosensitizer and Light Pave the Way for Cytosolic Targeting and Generation of Cytosolic CD8 T Cells Using PLGA Vaccine Particles

Peptide/protein vaccine delivery system based on PLGA particles

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