Bend Research Inc, 64550 Research Road, Bend, Oregon 97701, USA.
Pharm Res. 2013 Jan;30(1):257-68. doi: 10.1007/s11095-012-0870-x. Epub 2012 Sep 21.
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.
评估与透明质酸相互作用形成离子交联水凝胶的阳离子聚合物纳米粒子，以增加骨关节炎药物在关节腔内的腔内滞留时间。
体外试验包括使用注射器和膜溶解试验从交联水凝胶中释放纳米粒子、测量含有水凝胶的滑液的粘度以及在溶出试验中使用可水解酯键将模型活性物与阳离子取代的葡聚糖偶联以测量释放速率。使用荧光分子断层扫描术在体内测量关节内注射到大鼠膝关节后的纳米粒子保留情况。
在体外，从在滑液中形成的离子交联水凝胶中扩散和对流运输阳离子纳米粒子比不带电荷的纳米粒子慢。在体外，纳米粒子与滑液混合后形成的水凝胶不会明显改变滑液的粘度。从阳离子纳米粒子中释放的缀合肽每周约为 20%。在大鼠膝关节内注射后，1 周内有 70%的纳米粒子保留在关节中。
本研究证明了使用阳离子聚合物纳米粒子来增加治疗剂在关节中的保留时间的可行性，用于治疗骨关节炎等适应症。
