Development of Nanomedicines for Treatment of Posttraumatic Osteoarthritis
Abstract
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 endosomal/lysosomal 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2016
- Accession Number
- AD1008164
Entities
People
- Dong Wang
- P. E. Purdue
- Steven R. Goldring
Organizations
- University of Nebraska Omaha