Designing drug-free biodegradable nanoparticles to modulate inflammatory monocytes and neutrophils for ameliorating inflammation

Eiji Saito, Robert Kuo, Ryan M. Pearson, Nishant Gohel, Brandon Cheung, Nicholas J.C. King, Stephen D Miller, Lonnie D. Shea*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Inflammation associated with autoimmune diseases and chronic injury is an initiating event that leads to tissue degeneration and dysfunction. Inflammatory monocytes and neutrophils systemically circulate and enter inflamed tissue, and pharmaceutical based targeting of these cells has not substantially improved outcomes and has had side effects. Herein, we investigated the design of drug-free biodegradable nanoparticles, notably without any active pharmaceutical ingredient or targeting ligand, that target circulating inflammatory monocytes and neutrophils in the vasculature to inhibit them from migrating into inflamed tissue. Nanoparticles were formed from 50:50 poly(DL-lactide-co-glycolide) (PLG) with two molecular weights (Low, High) and poly(DL-lactide) (PLA) (termed PLG-L, PLG-H, and PDLA, respectively) and were analyzed for their association with monocytes and neutrophils and their impact on disease course along with immune cell trafficking. For particles injected intravenously for 6 consecutive days to mice with experimental autoimmune encephalomyelitis (EAE), PLG-H particles had significantly lower EAE clinical scores than PBS control, while PLG-L and PDLA particles had modest or negligible effect on EAE onset. In vivo and in vitro data suggests that PLG-H particles had high association with immune cells, with preferential association with blood neutrophils relative to other particles. PLG-H particles restrained immune cells from the central nervous system (CNS), with increased accumulation in the spleen, which was not observed for mice receiving PDLA or control treatments. These results demonstrate that the particle composition influences the association with inflammatory monocytes and neutrophils in the vasculature, with the potential to redirect trafficking and ameliorate inflammation.

Original languageEnglish (US)
Pages (from-to)185-196
Number of pages12
JournalJournal of Controlled Release
Volume300
DOIs
StatePublished - Apr 28 2019

Fingerprint

Nanoparticles
Monocytes
Neutrophils
Autoimmune Experimental Encephalomyelitis
Inflammation
Pharmaceutical Preparations
Polyglactin 910
Drug Design
Autoimmune Diseases
Spleen
Central Nervous System
Molecular Weight
Ligands
Wounds and Injuries
poly(lactide)

Keywords

  • Inflammation
  • Monocytes
  • Nanomedicine
  • Neutrophils
  • Poly(lactide-co-glycolide) nanoparticles

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Saito, Eiji ; Kuo, Robert ; Pearson, Ryan M. ; Gohel, Nishant ; Cheung, Brandon ; King, Nicholas J.C. ; Miller, Stephen D ; Shea, Lonnie D. / Designing drug-free biodegradable nanoparticles to modulate inflammatory monocytes and neutrophils for ameliorating inflammation. In: Journal of Controlled Release. 2019 ; Vol. 300. pp. 185-196.
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abstract = "Inflammation associated with autoimmune diseases and chronic injury is an initiating event that leads to tissue degeneration and dysfunction. Inflammatory monocytes and neutrophils systemically circulate and enter inflamed tissue, and pharmaceutical based targeting of these cells has not substantially improved outcomes and has had side effects. Herein, we investigated the design of drug-free biodegradable nanoparticles, notably without any active pharmaceutical ingredient or targeting ligand, that target circulating inflammatory monocytes and neutrophils in the vasculature to inhibit them from migrating into inflamed tissue. Nanoparticles were formed from 50:50 poly(DL-lactide-co-glycolide) (PLG) with two molecular weights (Low, High) and poly(DL-lactide) (PLA) (termed PLG-L, PLG-H, and PDLA, respectively) and were analyzed for their association with monocytes and neutrophils and their impact on disease course along with immune cell trafficking. For particles injected intravenously for 6 consecutive days to mice with experimental autoimmune encephalomyelitis (EAE), PLG-H particles had significantly lower EAE clinical scores than PBS control, while PLG-L and PDLA particles had modest or negligible effect on EAE onset. In vivo and in vitro data suggests that PLG-H particles had high association with immune cells, with preferential association with blood neutrophils relative to other particles. PLG-H particles restrained immune cells from the central nervous system (CNS), with increased accumulation in the spleen, which was not observed for mice receiving PDLA or control treatments. These results demonstrate that the particle composition influences the association with inflammatory monocytes and neutrophils in the vasculature, with the potential to redirect trafficking and ameliorate inflammation.",
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Designing drug-free biodegradable nanoparticles to modulate inflammatory monocytes and neutrophils for ameliorating inflammation. / Saito, Eiji; Kuo, Robert; Pearson, Ryan M.; Gohel, Nishant; Cheung, Brandon; King, Nicholas J.C.; Miller, Stephen D; Shea, Lonnie D.

In: Journal of Controlled Release, Vol. 300, 28.04.2019, p. 185-196.

Research output: Contribution to journalArticle

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AU - Saito, Eiji

AU - Kuo, Robert

AU - Pearson, Ryan M.

AU - Gohel, Nishant

AU - Cheung, Brandon

AU - King, Nicholas J.C.

AU - Miller, Stephen D

AU - Shea, Lonnie D.

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N2 - Inflammation associated with autoimmune diseases and chronic injury is an initiating event that leads to tissue degeneration and dysfunction. Inflammatory monocytes and neutrophils systemically circulate and enter inflamed tissue, and pharmaceutical based targeting of these cells has not substantially improved outcomes and has had side effects. Herein, we investigated the design of drug-free biodegradable nanoparticles, notably without any active pharmaceutical ingredient or targeting ligand, that target circulating inflammatory monocytes and neutrophils in the vasculature to inhibit them from migrating into inflamed tissue. Nanoparticles were formed from 50:50 poly(DL-lactide-co-glycolide) (PLG) with two molecular weights (Low, High) and poly(DL-lactide) (PLA) (termed PLG-L, PLG-H, and PDLA, respectively) and were analyzed for their association with monocytes and neutrophils and their impact on disease course along with immune cell trafficking. For particles injected intravenously for 6 consecutive days to mice with experimental autoimmune encephalomyelitis (EAE), PLG-H particles had significantly lower EAE clinical scores than PBS control, while PLG-L and PDLA particles had modest or negligible effect on EAE onset. In vivo and in vitro data suggests that PLG-H particles had high association with immune cells, with preferential association with blood neutrophils relative to other particles. PLG-H particles restrained immune cells from the central nervous system (CNS), with increased accumulation in the spleen, which was not observed for mice receiving PDLA or control treatments. These results demonstrate that the particle composition influences the association with inflammatory monocytes and neutrophils in the vasculature, with the potential to redirect trafficking and ameliorate inflammation.

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