The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees

Intra-articular injections are the most direct route for administering osteoarthritis (OA) therapies, yet how drug carriers distribute within the joint remains understudied. To this end, we developed a magnetic composite nanoparticle that can be tracked with fluorescence in vivo via an in vivo imagi...

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Published in:Journal of controlled release 2020-05, Vol.321, p.259-271
Main Authors: Partain, Brittany D., Unni, Mythreyi, Rinaldi, Carlos, Allen, Kyle D.
Format: Article
Language:English
Subjects:
Age
Electron paramagnetic resonance spectroscopy
Knee osteoarthritis
Magnetic nanoparticle
Superparamagnetic iron oxide
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description Intra-articular injections are the most direct route for administering osteoarthritis (OA) therapies, yet how drug carriers distribute within the joint remains understudied. To this end, we developed a magnetic composite nanoparticle that can be tracked with fluorescence in vivo via an in vivo imaging system (IVIS), and quantified ex vivo via electron paramagnetic resonance (EPR) spectroscopy. Using this particle, the effects of age and OA pathogenesis on particle clearance and distribution were evaluated in the medial meniscus transection model of OA (5-, 10-, and 15-month old male Lewis rats). At 9 weeks after meniscus transection, composite nanoparticles were injected and joint clearance was assessed via IVIS. At 2 weeks after injection, animals were euthanized and particle distribution was quantified ex vivo via EPR spectroscopy. IVIS and EPR spectroscopy data indicate a predominant amount of particles remained in the joint after 14 days. EPR spectroscopy data suggests particles cleared more slowly from OA knees than from the contralateral control, with particles clearing more slowly from 15-month old rats than from 5- and 10-month old rats. This study demonstrates the importance of including both age and OA as factors when evaluating nanoparticles for intra-articular drug delivery. [Display omitted] •Electron paramagnetic resonance spectroscopy can sensitively assess biodistribution.•Particles clear more slowly from OA knees compared to contralateral controls.•Intra-articular particle retention is increased in older animals.
doi_str_mv 10.1016/j.jconrel.2020.01.052
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This study demonstrates the importance of including both age and OA as factors when evaluating nanoparticles for intra-articular drug delivery. [Display omitted] •Electron paramagnetic resonance spectroscopy can sensitively assess biodistribution.•Particles clear more slowly from OA knees compared to contralateral controls.•Intra-articular particle retention is increased in older animals.</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2020.01.052</identifier><identifier>PMID: 32004585</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Age ; Electron paramagnetic resonance spectroscopy ; Knee osteoarthritis ; Magnetic nanoparticle ; Superparamagnetic iron oxide</subject><ispartof>Journal of controlled release, 2020-05, Vol.321, p.259-271</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. 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MU synthesized and characterized particles, conducted and analyzed colloidal stability experiments, assisted and trained BDP for EPR spectrometry experiments. KDA performed MMT surgeries. All authors contributed to the study design and data interpretation. The manuscript was drafted by BDP, with critical feedback and edits from MU, CR, and KDA. All authors agree with the content and interpretation of the data as presented.</notes><notes>1 Co-first authors.</notes><abstract>Intra-articular injections are the most direct route for administering osteoarthritis (OA) therapies, yet how drug carriers distribute within the joint remains understudied. To this end, we developed a magnetic composite nanoparticle that can be tracked with fluorescence in vivo via an in vivo imaging system (IVIS), and quantified ex vivo via electron paramagnetic resonance (EPR) spectroscopy. 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subjects Age
Electron paramagnetic resonance spectroscopy
Knee osteoarthritis
Magnetic nanoparticle
Superparamagnetic iron oxide
title The clearance and biodistribution of magnetic composite nanoparticles in healthy and osteoarthritic rat knees
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