Sacchetti Cristiano, Liu-Bryan Ru, Magrini Andrea, Rosato Nicola, Bottini Nunzio, Bottini Massimo
Inflammatory and Infectious Disease Center, Sanford Burnham Medical Research Institute , La Jolla, California 92037, United States.
ACS Nano. 2014 Dec 23;8(12):12280-91. doi: 10.1021/nn504537b. Epub 2014 Nov 26.
Osteoarthritis (OA) is a common and debilitating degenerative disease of articular joints for which no disease-modifying medical therapy is currently available. Inefficient delivery of pharmacologic agents into cartilage-resident chondrocytes after systemic administration has been a limitation to the development of anti-OA medications. Direct intra-articular injection enables delivery of high concentrations of agents in close proximity to chondrocytes; however, the efficacy of this approach is limited by the fast clearance of small molecules and biomacromolecules after injection into the synovial cavity. Coupling of pharmacologic agents with drug delivery systems able to enhance their residence time and cartilage penetration can enhance the effectiveness of intra-articularly injected anti-OA medications. Herein we describe an efficient intra-articular delivery nanosystem based on single-walled carbon nanotubes (SWCNTs) modified with polyethylene glycol (PEG) chains (PEG-SWCNTs). We show that PEG-SWCNTs are capable to persist in the joint cavity for a prolonged time, enter the cartilage matrix, and deliver gene inhibitors into chondrocytes of both healthy and OA mice. PEG-SWCNT nanoparticles did not elicit systemic or local side effects. Our data suggest that PEG-SWCNTs represent a biocompatible and effective nanocarrier for intra-articular delivery of agents to chondrocytes.
骨关节炎（OA）是一种常见且使人衰弱的关节退行性疾病，目前尚无改善病情的药物治疗方法。全身给药后，药物向软骨驻留软骨细胞的低效递送一直是抗OA药物开发的一个限制因素。直接关节内注射能够在软骨细胞附近递送高浓度药物；然而，这种方法的疗效受到注射到滑膜腔后小分子和生物大分子快速清除的限制。将药物与能够延长其驻留时间并增强软骨穿透能力的药物递送系统相结合，可以提高关节内注射抗OA药物的有效性。在此，我们描述了一种基于用聚乙二醇（PEG）链修饰的单壁碳纳米管（SWCNTs）的高效关节内递送纳米系统（PEG-SWCNTs）。我们表明，PEG-SWCNTs能够在关节腔内长时间存留，进入软骨基质，并将基因抑制剂递送至健康小鼠和OA小鼠的软骨细胞中。PEG-SWCNT纳米颗粒未引发全身或局部副作用。我们的数据表明，PEG-SWCNTs是一种用于向软骨细胞进行关节内递送药物的生物相容性且有效的纳米载体。
