Research Paper

Pharmaceutical Research

, Volume 30, Issue 1, pp 257-268

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Nanoparticles for Improved Local Retention after Intra-Articular Injection into the Knee Joint

  • Michael MorgenAffiliated withBend Research Inc. Email author 
  • , David TungAffiliated withBioMed Valley Discoveries
  • , Britton BorasAffiliated withDepartments of Medicine and Bioengineering, University of California—San Diego
  • , Warren MillerAffiliated withBend Research Inc.
  • , Anne-Marie MalfaitAffiliated withRush University Medical Center
  • , Micky TortorellaAffiliated withGuangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences



To evaluate using cationic polymeric nanoparticles that interact with hyaluronate to form ionically cross-linked hydrogels to increase the intra-articular retention time of osteoarthritis drugs in the synovial cavity.


In vitro tests included nanoparticle release from cross-linked hydrogels using syringe and membrane dissolution tests, viscosity measurement of synovial fluid containing hydrogels, and release-rate measurement for a model active conjugated to a cationically substituted dextran using a hydrolyzable ester linkage in a sink dissolution test. Nanoparticle retention after intra-articular injection into rat knees was measured in vivo using fluorescence molecular tomography.


Diffusional and convective transport of cationic nanoparticles from ionically cross-linked hydrogels formed in synovial fluid was slower in vitro than for uncharged nanoparticles. Hydrogels formed after the nanoparticles were mixed with synovial fluid did not appreciably alter the viscosity of the synovial fluid in vitro. In vitro release of a conjugated peptide from the cationic nanoparticles was approximately 20% per week. After intra-articular injection in rat knees, 70% of the nanoparticles were retained in the joint for 1 week.


This study demonstrates the feasibility of using cationic polymeric nanoparticles to increase the retention of therapeutic agents in articular joints for indications such as osteoarthritis.


cross-linked hydrogels increased retention intra-articular injection nanoparticles