Development of Nanomedicines for Treatment of Posttraumatic Osteoarthritis
Technical Report,05 Jun 2014,04 Dec 2015
University of Nebraska Omaha United States
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For this project, N-2-hydroxypropyl methacrylamide HPMA copolymer conjugates including dexamethasone and BMS-345541 conjugates were synthesized and labeled with near-infrared dye IRDye CW 800, Alexa Fluor 488 or Alexa Fluor 647. Mice with surgical destabilization of the medial meniscus DMM were established as an osteoarthritis model for our evaluation. P-IRDye and P-Alexa were given to the DMM mice via intraarticular injection. Optical imaging demonstrated that the DMM joints retained the injected P-IRDye. Fluorescence microscopy studies, in line with the in vivo imaging results, confirmed that P-Alexa was retained within the joint space and was primarily localized to synovial lining cells and articular chondrocytes. To further confirm the ability of chondrocytes to retain the copolymer conjugates, mouse femoral head explants were cultured in presence of P-Alexa. Imaging confirmed internalization of the conjugate by chondrocytes. Cell culture studies demonstrated that P-Alexa was sequestered within an endosomallysosomal compartment. Cell culture studies showed that P-BMS, a NF-B inhibitor copolymer conjugate, inhibited LPS induction of pro-inflammatory cytokine expression and provided sustained inhibition of osteoclast formation.