title: Polyethylene-glycol-modified single-walled carbon nanotubes for intra-articular delivery to chondrocytes.
abstract: Osteoarthritis (OA) is a common and debilitating degenerative disease of articular joints for which no disease-modifying medical therapy is currently available. Inefficient delivery of pharmacologic agents into cartilage-resident chondrocytes after systemic administration has been a limitation to the development of anti-OA medications. Direct intra-articular injection enables delivery of high concentrations of agents in close proximity to chondrocytes; however, the efficacy of this approach is limited by the fast clearance of small molecules and biomacromolecules after injection into the synovial cavity. Coupling of pharmacologic agents with drug delivery systems able to enhance their residence time and cartilage penetration can enhance the effectiveness of intra-articularly injected anti-OA medications. Herein we describe an efficient intra-articular delivery nanosystem based on single-walled carbon nanotubes (SWCNTs) modified with polyethylene glycol (PEG) chains (PEG-SWCNTs). We show that PEG-SWCNTs are capable to persist in the joint cavity for a prolonged time, enter the cartilage matrix, and deliver gene inhibitors into chondrocytes of both healthy and OA mice. PEG-SWCNT nanoparticles did not elicit systemic or local side effects. Our data suggest that PEG-SWCNTs represent a biocompatible and effective nanocarrier for intra-articular delivery of agents to chondrocytes.
authors.affiliation: Inflammatory and Infectious Disease Center, Sanford Burnham Medical Research Institute , La Jolla, California 92037, United States.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Sacchetti
authors.forename: Ru
authors.initials: R
authors.lastname: Liu-Bryan
authors.forename: Andrea
authors.initials: A
authors.lastname: Magrini
authors.forename: Nicola
authors.initials: N
authors.lastname: Rosato
authors.forename: Nunzio
authors.initials: N
authors.lastname: Bottini
authors.forename: Massimo
authors.initials: M
authors.lastname: Bottini
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D019902:Chondrocytes / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007596:Joints / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D060172:Morpholinos / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010003:Osteoarthritis / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D060172:Morpholinos; D037742:Nanotubes, Carbon; D049452:Green Fluorescent Proteins; D011092:Polyethylene Glycols
keywords: carbon nanotubes; chondrocytes; confocal microscopy; gene inhibition; intra-articular injection; morpholino antisense oligonucleotides; osteoarthritis