TY - JOUR
T1 - Designing drug-free biodegradable nanoparticles to modulate inflammatory monocytes and neutrophils for ameliorating inflammation
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.
N1 - Funding Information:
This work was supported by National Institute of Health (NIH) grants R01EB013198 (to L.D.S and S.D.M). We wish to thank the Flow Cytometry Core at the University of Michigan, Biomedical Research Core Facilities.
Funding Information:
This work was supported by National Institute of Health (NIH) grants R01EB013198 (to L.D.S and S.D.M). We wish to thank the Flow Cytometry Core at the University of Michigan, Biomedical Research Core Facilities.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/4/28
Y1 - 2019/4/28
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.
AB - 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.
KW - Inflammation
KW - Monocytes
KW - Nanomedicine
KW - Neutrophils
KW - Poly(lactide-co-glycolide) nanoparticles
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U2 - 10.1016/j.jconrel.2019.02.025
DO - 10.1016/j.jconrel.2019.02.025
M3 - Article
C2 - 30822435
AN - SCOPUS:85063353757
SN - 0168-3659
VL - 300
SP - 185
EP - 196
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -