title: Controlled release of anti-inflammatory peptides from reducible thermosensitive nanoparticles suppresses cartilage inflammation.
abstract: Characterized by pain, cartilage degradation, and inflammation, osteoarthritis is often treated with anti-inflammatory therapies that provide short-term relief but can have adverse side effects; intra-articular drug delivery systems with controlled release of anti-inflammatory peptides using degradable poly(N-isopropylacrylamide) (pNIPAM) nanoparticles could prolong relief and minimize these side effects. Nanoparticles provide a biocompatible drug carrier that can protect encapsulated therapeutics from enzymatic degradation and increase payload delivery upon encountering a degradation stimulus. Here we demonstrate passive targeting of inflamed cartilage ex vivo by uptake of PEGylated pNIPAM nanoparticles with degradable disulfide crosslinks (abbreviated as NGPEGSS) into chondrocytes and subsequent intracellular release of an anti-inflammatory peptide KAFAKLAARLYRKALARQLGVAA (KAFAK). The KAFAK-loaded NGPEGSS treatment reduced ex vivo inflammation to a greater extent compared to its non-degradable counterparts. This study highlights a nanoparticle system that delivers therapeutics intracellularly with improved efficacy by triggered degradation and suppresses inflammation in multiple cell types within an inflamed joint.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Jenny B
authors.initials: JB
authors.lastname: Lin
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Poh
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA. Electronic address: apanitch@purdue.edu.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Panitch
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002356:Cartilage / Q000187:drug effects / Q000473:pathology*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004337:Drug Carriers; D007249:Inflammation / Q000188:drug therapy; D053758:Nanoparticles; D010455:Peptides
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010455:Peptides
keywords: Anti-inflammatory peptides; Inflammation; N-isopropylacrylamide; Osteoarthritis; Thermosensitive polymer