SDF-1α in Glycan Nanoparticles Exhibits Full Activity and Reduces Pulmonary Hypertension in Rats

To establish a homing signal in the lung to recruit circulating stem cells for tissue repair, we formulated a nanoparticle, SDF-1α NP, by complexing SDF-1α with dextran sulfate and chitosan. The data show that SDF-1α was barely released from the nanoparticles over an extended period of time in vitro...

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Veröffentlicht in:Biomacromolecules 2013-11, Vol.14 (11), p.4009-4020
Hauptverfasser: Yin, Tao, Bader, Andrew R, Hou, Tim K, Maron, Bradley A, Kao, Derrick D, Qian, Ray, Kohane, Daniel S, Handy, Diane E, Loscalzo, Joseph, Zhang, Ying-Yi
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container_issue 11
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container_title Biomacromolecules
container_volume 14
creator Yin, Tao
Bader, Andrew R
Hou, Tim K
Maron, Bradley A
Kao, Derrick D
Qian, Ray
Kohane, Daniel S
Handy, Diane E
Loscalzo, Joseph
Zhang, Ying-Yi
description To establish a homing signal in the lung to recruit circulating stem cells for tissue repair, we formulated a nanoparticle, SDF-1α NP, by complexing SDF-1α with dextran sulfate and chitosan. The data show that SDF-1α was barely released from the nanoparticles over an extended period of time in vitro (3% in 7 days at 37 °C); however, incorporated SDF-1α exhibited full chemotactic activity and receptor activation compared to its free form. The nanoparticles were not endocytosed after incubation with Jurkat cells. When aerosolized into the lungs of rats, SDF-1α NP displayed a greater retention time compared to free SDF-1α (64 vs 2% remaining at 16 h). In a rat model of monocrotaline-induced lung injury, SDF-1α NP, but not free form SDF-1α, was found to reduce pulmonary hypertension. These data suggest that the nanoparticle formulation protected SDF-1α from rapid clearance in the lung and sustained its biological function in vivo.
doi_str_mv 10.1021/bm401122q
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source MEDLINE; ACS Publications
subjects Aerosols
Animals
Antihypertensive agents
Applied sciences
Biological and medical sciences
Cardiovascular system
Chemokine CXCL12 - administration & dosage
Chemokine CXCL12 - pharmacokinetics
Chemokine CXCL12 - pharmacology
Chemokine CXCL12 - therapeutic use
Chitosan - chemistry
Dextran Sulfate - chemistry
Exact sciences and technology
Forms of application and semi-finished materials
Humans
Hypertension, Pulmonary - chemically induced
Hypertension, Pulmonary - drug therapy
Hypertension, Pulmonary - prevention & control
Jurkat Cells
Male
Medical sciences
Miscellaneous
Monocrotaline
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Pharmacology. Drug treatments
Polymer industry, paints, wood
Polysaccharides - administration & dosage
Polysaccharides - chemistry
Rats
Rats, Sprague-Dawley
Technology of polymers
Time Factors
title SDF-1α in Glycan Nanoparticles Exhibits Full Activity and Reduces Pulmonary Hypertension in Rats
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