Designing drug-free biodegradable nanoparticles to modulate inflammatory monocytes and neutrophils for ameliorating inflammation.
Animals
Encephalomyelitis, Autoimmune, Experimental
/ chemically induced
Female
Inflammation
/ immunology
Mice
Monocytes
/ drug effects
Myelin Proteolipid Protein
Nanoparticles
/ administration & dosage
Neutrophils
/ drug effects
Peptide Fragments
Polyesters
/ administration & dosage
Polylactic Acid-Polyglycolic Acid Copolymer
/ administration & dosage
Spleen
/ immunology
Inflammation
Monocytes
Nanomedicine
Neutrophils
Poly(lactide-co-glycolide) nanoparticles
Journal
Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908
Informations de publication
Date de publication:
28 04 2019
28 04 2019
Historique:
received:
20
12
2018
revised:
14
02
2019
accepted:
19
02
2019
pubmed:
2
3
2019
medline:
2
7
2020
entrez:
2
3
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30822435
pii: S0168-3659(19)30108-7
doi: 10.1016/j.jconrel.2019.02.025
pmc: PMC6486651
mid: NIHMS1525236
pii:
doi:
Substances chimiques
Myelin Proteolipid Protein
0
Peptide Fragments
0
Polyesters
0
myelin proteolipid protein (139-151)
0
Polylactic Acid-Polyglycolic Acid Copolymer
1SIA8062RS
poly(lactide)
459TN2L5F5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
185-196Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK020572
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB013198
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS099334
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM105538
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.
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