Objective

Intra-articular drug delivery holds great promise for the treatment of joint diseases such as osteoarthritis. The objective of this study was to evaluate the TAT peptide transduction domain (TAT-PTD) as a potential intra-articular drug delivery technology for synovial joints.

Design

Experiments examined the ability of TAT conjugates to associate with primary chondrocytes and alter cellular function both in vitro and in vivo. Further experiments examined the ability of the TAT-PTD to bind to human osteoarthritic cartilage.

Results

The results show that the TAT-PTD associates with chondrocytes, is capable of delivering siRNA for chondrocyte gene knockdown, and that the recombinant enzyme TAT-Cre is capable of inducing in vivo genetic recombination within the knee joint in a reporter mouse model. Last, binding studies show that osteoarthritic cartilage preferentially uptakes the TAT-PTD from solution.

Conclusions

The results suggest that the TAT-PTD is a promising delivery strategy for intra-articular therapeutics.

中文翻译：

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TAT 蛋白转导域作为关节内给药技术。

客观的

关节内给药对于治疗骨关节炎等关节疾病具有很大的前景。本研究的目的是评估 TAT 肽转导结构域 (TAT-PTD) 作为滑膜关节的潜在关节内给药技术。

设计

实验检查了 TAT 缀合物与原代软骨细胞结合并在体外和体内改变细胞功能的能力。进一步的实验检查了 TAT-PTD 与人类骨关节炎软骨结合的能力。

结果

结果表明，TAT-PTD 与软骨细胞结合，能够为软骨细胞基因敲除提供 siRNA，并且重组酶 TAT-Cre 能够在报告小鼠模型中诱导膝关节内的体内基因重组。最后，结合研究表明骨关节炎软骨优先吸收溶液中的 TAT-PTD。

结论

结果表明，TAT-PTD 是一种有前途的关节内治疗递送策略。