Delivery of anti-inflammatory peptides from hollow PEGylated poly(NIPAM) nanoparticles reduces inflammation in an ex vivo osteoarthritis model

Journal of Controlled Release : Official Journal of the Controlled Release Society
James McMastersAlyssa Panitch

Abstract

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, non-invasive 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-2-methyl-1-propanesulfonic acid (AMPSA) was copolymerized in the shell to increase passive loading of an anti-inflammatory 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-1β) stimulation. This thermosensitive hollow nanoparticle system provides an excellent platform for the delivery of peptide therapeutics into highly proteolytic environments such as osteoarthritis.

Citations

Dec 4, 2019·Journal of Biomedical Materials Research. Part a·Eunjae ParkRamkumar T Annamalai
Jan 28, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Zengming ZhengJian Xiao
Dec 29, 2020·Frontiers in Aging Neuroscience·Robert A Culibrk, Mariah S Hahn
Mar 9, 2021·Frontiers in Bioengineering and Biotechnology·Huailan WangSifeng Tao
Mar 13, 2021·Biomedical Materials·Xueli MeiElizabeth R Gillies

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