title: Electrostatic interactions enable rapid penetration, enhanced uptake and retention of intra-articular injected avidin in rat knee joints.
abstract: Intra-articular (i.a.) drug delivery for local treatment of osteoarthritis remains inadequate due to rapid clearance by the vasculature or lymphatics. Local therapy targeting articular cartilage is further complicated by its dense meshwork of collagen and negatively charged proteoglycans, which can prevent even nano-sized solutes from entering. In a previous in vitro study, we showed that Avidin, due to its size (7 nm diameter) and high positive charge (pI 10.5), penetrated the full thickness of bovine cartilage and was retained for 15 days. With the goal of using Avidin as a nano-carrier for cartilage drug delivery, we investigated its transport properties within rat knee joints. Avidin penetrated the full thickness of articular cartilage within 6 h, with a half-life of 29 h, and stayed inside the joint for 7 days after i.a. injection. The highest concentration of Avidin was found in cartilage, the least in patellar tendon and none in the femoral bone; in contrast, negligible Neutravidin (neutral counterpart of Avidin) was present in cartilage after 24 h. A positive correlation between tissue sGAG content and Avidin uptake (R(2)  = 0.83) confirmed the effects of electrostatic interactions. Avidin doses up to at least 1 µM did not affect bovine cartilage explant cell viability, matrix catabolism or biosynthesis.
authors.affiliation: Department of Mechanical Engineering, MIT, 77 Massachusetts Avenue, Cambridge, Massachusetts, 02139; Center for Biomedical Engineering, MIT, 77 Massachusetts Avenue, Cambridge, Massachusetts, 02139.
authors.forename: Ambika G
authors.initials: AG
authors.lastname: Bajpayee
authors.forename: Maximiliano
authors.initials: M
authors.lastname: Scheu
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Grodzinsky
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Porter
mesh_terms: D000818:Animals; D001360:Avidin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage*; D006025:Glycosaminoglycans / Q000378:metabolism; D006207:Half-Life; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000378:metabolism*; D008022:Ligaments / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D055672:Static Electricity; D013710:Tendons / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D006025:Glycosaminoglycans; C093483:neutravidin; D001360:Avidin
keywords: Avidin; cartilage; glycosaminoglycans; intra-articular drug delivery; rat