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

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.

Intra-articular injection of kartogenin-conjugated polyurethane nanoparticles attenuates the progression of osteoarthritis

“…Therefore, development of IA drug delivery systems that can provide sustained release is helpful for successful OA treatment. Several drug delivery systems, such as hydrogel (Singh et al., 2014 ), liposomes (Stalder & Zumbuehl, 2017 ), nanoparticles (McMasters et al., 2017 ), and microparticles (Arunkumar et al., 2016 ), have been used to achieve sustained release of drugs in joints. In this study, amphiphilic polyurethane with pendant amino group was synthesized to form covalent bonds between the amine group of PN and carboxyl group of KGN, which contribute to sustained and controlled release of KGN in vitro .…”

Polymerized-Type I Collagen Induces a High Quality Cartilage Repair in a Rat Model of Osteoarthritis

“…At the present time is widely accepted that OA results from an admixture of changes occurring throughout the joint tissues, including cartilage, synovium, ligament, and bone and that inflammation is a key player in the progression of cartilage destruction and joint disease [29,30]. Increased levels of proinflammatory cytokines are frequently present in the synovial fluid and tissues of OA-affected joints, particularly, IL-1β and TNF-α directly contribute to reduced anabolic and enhanced catabolic activities in OA-affected joints through regulation of proteases expression that acts to degrade cartilage [2,24,31].…”

Recent advances in the bioanalytical methods of polyethylene glycols and PEGylated pharmaceuticals

“…Up to present, there are about 20 marketed PEGylated pharmaceutics, including PEGylated small MW drugs (Naloxegol and PEG‐doxorubicin) [27–30], PEGylated proteins, and monoclonal antibodies (peginterferon alfa‐2a, peginterferon alfa‐2b, peginterferon beta‐1a, pegaptanib, pegaspargase, mPEG‐Epoetin beta, pegfilgrastim, pegteograstim, pegloticase, pegvaliase, pegvisomant, certolizumab pegol, calaspargase pegol, PEG‐antihemophilic factor, PEG‐coagulation factor IX, and PEG‐adenosine deaminase bovine etc .) [31–34], as to PEGylated nanoparticles (Doxil) [35–39]. It was reported that PEGylated drugs may also possess enhanced permeability and retention (EPR) effect, which will benefit the PEG‐modified drugs accumulating in the tumor tissue [40].…”