Development of a nanoparticulate formulation of retinoic acid that suppresses Th17 cells and upregulates regulatory T cells

Capurso, Noah A.; Look, Michael; Jeanbart, Laura; Nowyhed, Heba; Abraham, Clara; Craft, Joe; Fahmy, Tarek M.

doi:10.4161/self.1.4.13946

Cited by 23 publications

(22 citation statements)

References 38 publications

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“…48 The ability of nanoparticulate ATRA to suppress Th17 cells and induce regulatory T-cells in vitro has already been reported. 49 In addition, the efficacy of ATRA alone in IBD models is well established. By using mice that overproduce tumour necrosis factor [TNF] and develop chronic ileitis [TNFΔARE mice], Collins and colleagues 50 showed that twice-weekly ATRA injections (300 μg given intraperitoneally [IP]) significantly attenuated established disease by increasing the number and function of CD103+ DCs and regulatory T-cells while reducing Th17 cells.…”

Section: Discussionmentioning

confidence: 99%

Oral Delivery of Particulate Transforming Growth Factor Beta 1 and All-Trans Retinoic Acid Reduces Gut Inflammation in Murine Models of Inflammatory Bowel Disease

Conway

Hammer²,

Furtado

et al. 2015

ECCOJC

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Conclusions: Both agents given together outperformed either separately. Highest TGFβ doses and most frequent dose schedule were most effective. Activity was associated with a significant increase [45%] in Foxp3 expression by colonic lamina propria CD4+ CD25+ T-cells. Activity was also demonstrated in dextran sulphate sodium-induced colitis. The data support development of the combination product as a novel, targeted immune based therapy for treatment for IBD.

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Section: Discussionmentioning

confidence: 99%

Oral Delivery of Particulate Transforming Growth Factor Beta 1 and All-Trans Retinoic Acid Reduces Gut Inflammation in Murine Models of Inflammatory Bowel Disease

Conway

Hammer²,

Furtado

et al. 2015

ECCOJC

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“…Numerous researchers around the world have reported the biomimetic micro-and nanoparticles (MNPs) carrying myelin peptides or proteins along with toxin or regulatory molecules for the treatment of EAE or MS (30,40,41). s.c. prophylactic and therapeutic vaccination with PLGA NPs encapsulating MOG 35-55 peptide and IL-10 ameliorated the MOG-induced EAE in mice (42).…”

Section: Discussionmentioning

confidence: 99%

A Tolerogenic Artificial APC Durably Ameliorates Experimental Autoimmune Encephalomyelitis by Directly and Selectively Modulating Myelin Peptide–Autoreactive CD4+ and CD8+ T Cells

Wan

Pei

Shahzad

et al. 2018

The Journal of Immunology

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In this study, a tolerogenic artificial APC (TaAPC) was developed to directly and selectively modulate myelin-autoreactive CD4 and CD8 T cells in the myelin oligodendrocyte glycoprotein (MOG) peptide-induced experimental autoimmune encephalomyelitis in C57BL/6J mice. Cell-sized polylactic-coglycolic acid microparticles were generated to cocouple target Ags (MOG/H-2D-Ig dimer, MOG/I-A multimer), regulatory molecules (anti-Fas and PD-L1-Fc), and "self-marker" CD47-Fc and encapsulate inhibitory cytokine (TGF-β1). Four infusions of the TaAPCs markedly and durably inhibited the experimental autoimmune encephalomyelitis progression and reduced the local inflammation in CNS tissue. They circulated throughout vasculature into peripheral lymphoid tissues and various organs, but not into brain, with retention of 36 h and exerted direct effects on T cells in vivo and in vitro. Two infusions of the TaAPCs depleted 65-79% of MOG-specific CD4 and 46-62% of MOG-specific CD8 T cells in peripheral blood, spleen, and CNS tissues in an Ag-specific manner and regulatory molecule-dependent fashion; induced robust T cell apoptosis; inhibited the activation and proliferation of MOG peptide-reactive T cells; reduced MOG peptide-reactive Th1, Th17, and Tc17 cells; and expanded regulatory T cells. They also inhibited IFN-γ/IL-17A secretion and elevated IL-10/TGF-β1 production in splenocytes but not in CNS tissue. More importantly, the TaAPCs treatment did not obviously suppress the overall immune function of host. To our knowledge, this study provides the first experimental evidence for the capability of TaAPCs to directly modulate autoreactive T cells by surface presentation of multiple ligands and paracrine release of cytokine, thus suggesting a novel Ag-specific immunotherapy for the T cell-mediated autoimmune diseases.

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“…Such prolonged circulation effect of uncoated BC-PLGA-NPs was reported by Tsai et al 13 using curcumin-encapsulated uncoated PLGA-NPs (approximately 160 nm in diameter). Considering the release profile, Capurso et al 10 prepared retinoic acid-encapsulated PLGA-NPs (approximately 250 nm in diameter) with a similar procedure to us. They found 20% of retinoic acid was released from PLGA-NPs within 10 hours of incubation in phosphate-buffered saline.…”

Section: Discussionmentioning

confidence: 99%

“…Preparation of Bc-Plga-NPs: surface morphology and ee analysis BC-PLGA-NPs were prepared by solvent evaporation. 10,11 Briefly, 20 mg of free (commercial) BC powder and 200 mg of followed by IV administration of 2.4 mL of PS80-coated BC-PLGA-NPs suspension, uncoated BC-PLGA-NPs suspension, or control saline into the rat tail vein, at a BC dose of 8.5 mg/rat (equivalent sum of BC from the three preparations). Rats were sacrificed by decapitation 1 hour after administration, and organs (brain, heart, liver, lungs, and spleen) were harvested.…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

Distribution of β-carotene-encapsulated polysorbate 80-coated poly(D, L-lactide-co-glycolide) nanoparticles in rodent tissues following intravenous administration

Miyazawa¹,

Nakagawa²,

Harigae³

et al. 2015

IJN

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PurposeBiodegradable nanoparticles (NPs) composed of poly(D, L-lactide-co-glycolide) (PLGA) have attracted considerable attention as delivery systems of drugs and antioxidative compounds, such as β-carotene (BC). Intravenous (IV) administration of BC-containing PLGA-NPs (BC-PLGA-NPs) coated with polysorbate 80 (PS80) has been shown to effectively deliver BC to the brain. However, the whole-body distribution profile of BC is still not clear. Therefore, we investigated the accumulation of BC in various organs, including the brain, following IV administration of PS80-coated BC-PLGA-NPs in rats.MethodsPS80-coated and uncoated BC-PLGA-NPs were prepared by solvent evaporation, and administered intravenously to Sprague Dawley rats at a BC dose of 8.5 mg/rat. Accumulation of BC in various organs (brain, heart, liver, lungs, and spleen) and blood plasma was evaluated by high performance liquid chromatography with ultraviolet (UV) detection, 1 hour after administration.ResultsWe prepared PS80-coated BC-PLGA-NPs with an entrapment efficiency of 14%, a particle size of 260 nm, and a zeta potential of −26 mV. Coating with PS80 was found to result in significant accumulation of BC in the lungs, rather than in the brain and other tissues. Further, plasma levels of BC in the PS80-coated BC-PLGA-NP group were much lower than those of the uncoated BC-PLGA-NP group.ConclusionFollowing IV administration, PS80-coated BC-PLGA-NPs are quickly transferred from plasma circulation to the lungs, rather than the brain. Significant accumulation of BC in the lungs may be useful for health-related applications.

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Development of a nanoparticulate formulation of retinoic acid that suppresses Th17 cells and upregulates regulatory T cells

Cited by 23 publications

References 38 publications

Oral Delivery of Particulate Transforming Growth Factor Beta 1 and All-Trans Retinoic Acid Reduces Gut Inflammation in Murine Models of Inflammatory Bowel Disease

Oral Delivery of Particulate Transforming Growth Factor Beta 1 and All-Trans Retinoic Acid Reduces Gut Inflammation in Murine Models of Inflammatory Bowel Disease

A Tolerogenic Artificial APC Durably Ameliorates Experimental Autoimmune Encephalomyelitis by Directly and Selectively Modulating Myelin Peptide–Autoreactive CD4+ and CD8+ T Cells

Distribution of β-carotene-encapsulated polysorbate 80-coated poly(D, L-lactide-co-glycolide) nanoparticles in rodent tissues following intravenous administration

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Development of a nanoparticulate formulation of retinoic acid that suppresses Th17 cells and upregulates regulatory T cells

Cited by 23 publications

References 38 publications

Oral Delivery of Particulate Transforming Growth Factor Beta 1 and All-Trans Retinoic Acid Reduces Gut Inflammation in Murine Models of Inflammatory Bowel Disease

Oral Delivery of Particulate Transforming Growth Factor Beta 1 and All-Trans Retinoic Acid Reduces Gut Inflammation in Murine Models of Inflammatory Bowel Disease

A Tolerogenic Artificial APC Durably Ameliorates Experimental Autoimmune Encephalomyelitis by Directly and Selectively Modulating Myelin Peptide–Autoreactive CD4+ and CD8+ T Cells

Distribution of &beta;-carotene-encapsulated polysorbate 80-coated poly(D, L-lactide-co-glycolide) nanoparticles in rodent tissues following intravenous administration

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Distribution of β-carotene-encapsulated polysorbate 80-coated poly(D, L-lactide-co-glycolide) nanoparticles in rodent tissues following intravenous administration