Journal
JOURNAL OF CONTROLLED RELEASE
Volume 258, Issue -, Pages 161-170Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.05.008
Keywords
N-isopropylacrylamide; Thermosensitive polymer; Anti-inflammatory peptides; Inflammation; Osteoarthritis
Funding
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R01AR065398]
- Institute of Diabetes and Digestive and Kidney Diseases [T32DK101001]
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Targeted delivery of anti-inflammatory osteoarthritis treatments have the potential to significantly decrease undesirable systemic side effects and reduce required therapeutic dosage. Here we present a targeted, noninvasive drug delivery system to decrease inflammation in an osteoarthritis model. Hollow thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) nanoparticles have been synthesized via degradation of a N, N'-bis (acryloyl) cystamine (BAC) cross-linked core out of a non-degradable pNIPAM shell. Sulfated 2-acrylamido-2methyl- 1-propanesulfonic acid (AMPSA) was copolymerized in the shell to increase passive loading of an antiinflammatory mitogen-activated protein kinase-activated protein kinase 2 (MK2)-inhibiting cell-penetrating peptide (KAFAK). The drug-loaded hollow nanoparticles were effective at delivering a therapeutically active dose of KAFAK to bovine cartilage explants, suppressing pro-inflammatory interleukin-6 (IL-6) expression after interleukin-1 beta (IL-1 beta) stimulation. This thermosensitive hollow nanoparticle system provides an excellent platform for the delivery of peptide therapeutics into highly proteolytic environments such as osteoarthritis.
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