Translational Nanobiomaterials and Imaging (TNI) Group, Radiology Department, Leiden University Medical Centrum, Leiden, The Netherlands; Percuros, Enschede, The Netherlands.
Translational Nanobiomaterials and Imaging (TNI) Group, Radiology Department, Leiden University Medical Centrum, Leiden, The Netherlands.
J Control Release. 2019 Sep 10;309:265-276. doi: 10.1016/j.jconrel.2019.07.031. Epub 2019 Jul 27.
This study focuses on intra-articular (IA) drug delivery system for the treatment of knee osteoarthritis (OA). In osteoarthritic condition the synovial fluid presents pockets with lower pH environment. To take advantage of these pH differences, poly(lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and pH- responsive PLGA NPs encapsulated with ammonium bicarbonate (NHHCO) were generated. The nanoparticles were loaded with hyaluronic acid (HA) as a possible model drug for OA and with near-infrared dye (NIR) that was used to visualize the NPs with molecular imaging techniques. These NPs were characterized by dynamic light scattering, transmission electron microscopy and compared in in vitro, in vivo and ex vivo experiments in the treatment of OA. The results indicate that the NPs were sufficiently small, displayed a uniform size distribution and were non-toxic both in vitro and in vivo. Both NPs treatment seem to induced a reduction in OA progression, with pH- responsive NPs showing the more pronounced effect. This is probably because the pockets of low pH environment in the synovial fluid trigger a burst release of the pH-responsive NPs. This result is corroborated by in vitro experiments since the pH- responsive NPs showed an extracellular burst release behavior and higher chondrocyte vitality than non-responsive NPs. This study demonstrates that PLGA NPs containing HA and NHHCO are candidates for the treatment of knee OA.
本研究专注于关节内（IA）药物传递系统治疗膝骨关节炎（OA）。在骨关节炎条件下，滑液呈现出 pH 值较低的环境的小囊。为了利用这些 pH 值差异，生成了聚（乳酸-共-乙醇酸）（PLGA）纳米颗粒（NPs）和 pH 响应的 PLGA NPs，其内部封装了碳酸氢铵（NHHCO）。这些纳米颗粒负载透明质酸（HA）作为 OA 的可能模型药物，并负载近红外染料（NIR），以便使用分子成像技术可视化 NPs。通过动态光散射、透射电子显微镜对这些 NPs 进行了表征，并在 OA 的体外、体内和离体实验中进行了比较。结果表明， NPs 足够小，显示出均匀的粒径分布，在体外和体内均无毒性。两种 NPs 治疗似乎都能诱导 OA 进展的减少，其中 pH 响应 NPs 表现出更明显的效果。这可能是因为滑液中的低 pH 值环境小囊触发了 pH 响应 NPs 的爆发式释放。体外实验证实了这一结果，因为 pH 响应 NPs 表现出细胞外爆发释放行为，并且对软骨细胞的活力高于非响应 NPs。本研究表明，载有 HA 和 NHHCO 的 PLGA NPs 是治疗膝 OA 的候选药物。
