, Volume 19, Issue 2, pp 132-139

Size-Dependency of DL-Lactide/Glycolide Copolymer Particulates for Intra-Articular Delivery System on Phagocytosis in Rat Synovium

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Purpose. The present study evaluated the size-dependency of DL-lactide/glycolide copolymer (PLGA) particulates for an intra-articular delivery system on phagocytosis in the rat synovium after administering directly into the joint cavity. We also investigated the biocompatibility of PLGA particulate systems administered directly into the joint cavity of the rat.

Methods. Fluoresceinamine bound PLGA (FA-PLGA) nanospheres and microspheres were prepared by the modified emulsion solvent diffusion method. The suspension of these particulate systems was administered into the rat-joint cavity and the biological action of the synovium was evaluated by histological inspection and fluorescence microscopy.

Results. A colloidal suspension of the FA-PLGA nanospheres, with a mean diameter of 265 nm, was phagocytosed in the synovium by the macrophages infiltrated through the synovial tissues. The phagocytosed nanospheres were delivered to the deep underlying tissues. An aqueous suspension of the FA-PLGA microspheres, with a mean diameter of 26.5 μm, was not phagocytosed in the macrophages. The macrophages slightly proliferated in the epithelial lining synovial-cells and the microspheres were covered with a granulation of multinucleated giant cells. The molecular weights of the polymer in these particulate systems were slowly reduced in the synovium. Localized inflammatory responses were almost undetected.

Conclusions. PLGA nanospheres should be more suitable for delivery to inflamed synovial tissue than microspheres due to their ability to penetrate the synovium. PLGA particulate systems with biocompatibility in the joint can provide local-therapy action in joint diseases in a different manner depending on the size of the system.