Cationic PLGA/Eudragit RL nanoparticles for increasing retention time in synovial cavity after intra-articular injection in knee joint.
Cationic PLGA/Eudragit RL nanoparticles for increasing retention time in synovial cavity after intra-articular injection in knee joint.
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DOI：
10.2147/ijn.s88363
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发表时间：
2015
影响因子：
8
通讯作者：
Kang MJ
中科院分区：
文献类型：
--
作者：
Kim SR;Ho MJ;Lee E;Lee JW;Choi YW;Kang MJ
表面带正电的聚乳酸-羟基乙酸酯(PLGA)/Eudragit RL纳米颗粒（NPs）通过与透明质酸（滑膜液中大量存在的内源性阴离子多糖）形成微米大小的静电聚集体，旨在增加关节内注射后关节内的滞留时间并维持释放。采用溶剂蒸发法制备了PLGA、Eudragit RL和聚乙烯醇组成的阳离子NPs。NPs的尺寸为170.1 nm，在磷酸盐缓冲盐水中的zeta电位为21.3 mV。高光谱成像（CytoViva®）显示，由于NPs和多糖之间的静电相互作用，在混合后形成微米大小的丝状聚集体。携带荧光探针（1,1 ' -二十八烷基-3,3,3 ‘,3 ’四甲基lindotricarbocyanine iodiine， DiR）的NPs在膝关节中的滞留时间明显延长，注射后28天荧光信号保存超过50%。在小鼠关节内注射DiR溶液后，荧光水平在3天内迅速下降到初始浓度的30%。根据这些发现，我们认为基于plga的阳离子NPs可能是一种有前途的工具，可以选择性地延长关节治疗药物的递送时间。
Positively surface-charged poly(lactide-co-glycolide) (PLGA)/Eudragit RL nanoparticles (NPs) were designed to increase retention time and sustain release profile in joints after intra-articular injection, by forming micrometer-sized electrostatic aggregates with hyaluronic acid, an endogenous anionic polysaccharide found in high amounts in synovial fluid. The cationic NPs consisting of PLGA, Eudragit RL, and polyvinyl alcohol were fabricated by solvent evaporation technique. The NPs were 170.1 nm in size, with a zeta potential of 21.3 mV in phosphate-buffered saline. Hyperspectral imaging (CytoViva®) revealed the formation of the micrometer-sized filamentous aggregates upon admixing, due to electrostatic interaction between NPs and the polysaccharides. NPs loaded with a fluorescent probe (1,1′-dioctadecyl-3,3,3′,3′ tetramethylindotricarbocyanine iodide, DiR) displayed a significantly improved retention time in the knee joint, with over 50% preservation of the fluorescent signal 28 days after injection. When DiR solution was injected intra-articularly, the fluorescence levels rapidly decreased to 30% of the initial concentration within 3 days in mice. From these findings, we suggest that PLGA-based cationic NPs could be a promising tool for prolonged delivery of therapeutic agents in joints selectively.