Timothy K Mwangi1, Robby D Bowles1, David M Tainter2, Richard D Bell2, David L Kaplan3, Lori A Setton4. 1. Department of Biomedical Engineering, Duke University, Durham, NC, United States. 2. Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, United States. 3. Department of Biomedical Engineering, Tufts University, Medford, MA, United States. 4. Department of Biomedical Engineering, Duke University, Durham, NC, United States; Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, United States. Electronic address: lori.setton@duke.edu.
Abstract
OBJECTIVE: To determine the utility of silk fibroin (SF) microparticles as sustained release vehicles for intra-articular delivery. DESIGN: SF formulations were varied to generate microparticle drug carriers that were characterized in vitro for their physical properties, release kinetics for a conjugated fluorophore (Cy7), and in vivo for intra-articular retention time using live-animal, fluorescence in vivo imaging. RESULTS: SF microparticle carriers were spherical in shape and ranged from 598 nm to 21.5 μm in diameter. SF microparticles provided for sustained release of Cy7 in vitro, with only 10% of the initial load released over 7 days. Upon intra-articular injection in rat knee joints, the SF microparticles were associated with an intra-articular fluorescence decay half-life of 43.3h, greatly increasing the joint residence over that for an equivalent concentration of SF-Cy7 in solution form. The SF microparticles also increase the localization of dye within the joint cavity as determined by image analysis of fluorescent gradients, significantly reducing distribution of the Cy7 to neighboring tissue as compared to SF-Cy7 in free solution. CONCLUSION: Silk microparticles act to provide for localized and sustained delivery of loaded small molecules following intra-articular injection, and may be an attractive strategy for delivering small molecule drugs for the treatment of arthritis.
OBJECTIVE: To determine the utility of silk fibroin (SF) microparticles as sustained release vehicles for intra-articular delivery. DESIGN: SF formulations were varied to generate microparticle drug carriers that were characterized in vitro for their physical properties, release kinetics for a conjugated fluorophore (Cy7), and in vivo for intra-articular retention time using live-animal, fluorescence in vivo imaging. RESULTS: SF microparticle carriers were spherical in shape and ranged from 598 nm to 21.5 μm in diameter. SF microparticles provided for sustained release of Cy7 in vitro, with only 10% of the initial load released over 7 days. Upon intra-articular injection in rat knee joints, the SF microparticles were associated with an intra-articular fluorescence decay half-life of 43.3h, greatly increasing the joint residence over that for an equivalent concentration of SF-Cy7 in solution form. The SF microparticles also increase the localization of dye within the joint cavity as determined by image analysis of fluorescent gradients, significantly reducing distribution of the Cy7 to neighboring tissue as compared to SF-Cy7 in free solution. CONCLUSION: Silk microparticles act to provide for localized and sustained delivery of loaded small molecules following intra-articular injection, and may be an attractive strategy for delivering small molecule drugs for the treatment of arthritis.
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