Eicosapentanoic acid (EPA) is an antioxidant and omega‐3 polyunsaturated fatty acid that reduces inflammatory cytokine production. Gelatin hydrogel can be used as a carrier of a physiologically active substance that release it gradually for an average of ~3 weeks. Therefore, this study aimed to clarify the effect of EPA‐incorporating gelatin hydrogels on osteoarthritis (OA) progression in vivo. Ten‐week‐old male C57BL/6J mice were randomly divided into six groups (n = 6): Sham, destabilization of the medial meniscus (DMM), Corn: DMM + 2 µL corn oil, EPA injection alone (EPA‐I): DMM + 2 µL corn oil + 125 μg/μL EPA, Gel: DMM + gelatin hydrogels, and EPA‐G: DMM + 125 μg/μL EPA‐incorporating gelatin hydrogels. The mice were euthanized at 8 weeks after DMM or Sham surgery, and subjected to histological evaluation. Matrix‐metalloproteinases‐3 (MMP‐3), MMP‐13, interleukin‐1β (IL‐1β), p‐IKK α/β, CD86, and CD163 protein expression in the synovial cartilage was detected by immunohistochemical staining. F4/80 expression was also assessed using the F4/80 score of macrophage. Histological score was significantly lower in EPA‐G than in EPA‐I. MMP‐3‐, MMP‐13‐, IL‐1β‐, and p‐IKK α/β‐positive cell ratio was significantly lower in EPA‐G than in EPA‐I. However, CD86‐ and CD163‐positive cell ratio was not significantly different between EPA‐I and EPA‐G. The average‐sum F4/80 score of macrophage in EPA‐G was significantly lower than that in EPA‐I. EPA‐incorporating gelatin hydrogels were shown to prevent OA progression in vivo more effectively than EPA injection alone. Our results suggested that intra‐articular administration of controlled‐release EPA can be a new therapeutic approach for treating OA.
The objective of this study is to investigate the autophagy activity of cells by the intracellular release of rapamycin (Rapa) of an autophagy inducer. Rapa was incorporated into nanospheres of poly (lactic-co-glycolic acid) (PLGA) for the controlled release of Rapa. Rapa was released from the PLGA nanospheres incorporating rapamycin (Rapa-PLGA-NS) with time while the Rapa-PLGA-NS were hydrolytically degraded. When human hepatocellular carcinoma (HepG2) cells were incubated with the Rapa-PLGA-NS, the Rapa-PLGA-NS were internalized, and the intracellular concentration was maintained over four days, indicating the intracellular Rapa release. The microtubule-associated protein 1 light chain (LC3) of an autophagy marker was significantly high for the Rapa-PLGA-NS group compared with the free Rapa group even after four days incubation. In addition, intracellular harmful ubiquitinated proteins were degraded by the intracellular release of Rapa even after four days incubation in contrast to free Rapa. It is concluded that the intracellular Rapa release is effective in modulating the autophagy activity over a longer time period.
Background Eicosapentanoic acid (EPA) is an antioxidant and omega-3 polyunsaturated fatty acid that reduces inflammatory cytokine production. Gelatin hydrogel is a release technology that contains a physiologically active substance and releases the substance gradually for an average of ~3 weeks. Therefore, this study aimed to investigate the effect of EPA-incorporating gelatin hydrogels on osteoarthritis (OA) progression in vivo . Methods Ten-week-old male C57BL/6J mice were randomly divided into six groups (six mice each): sham, destabilization of the medial meniscus (DMM), Corn (DMM + 2 µl corn oil), EPA-I (DMM + 2 µl corn oil + 3 mg/ml EPA), Control (DMM + control gelatin hydrogels), and EPA-G (DMM + 3 mg/ml EPA-incorporating gelatin hydrogels) groups. Mice were then euthanized 8 weeks after DMM or sham surgery, and subjected to histological evaluation. Furthermore, MMP-3, MMP-13, IL-1β, p-IKK α/β, CD86, and CD163 was detected by immunohistochemical staining. F4/80 expression was also assessed using the F4/80 score of synovitis. Results Histologic score was significantly improved in EPA-G compared to in EPA-I. MMP-3-, MMP-13-, IL-1β-, and p-IKK α/β-positive cell ratio was significantly improved in EPA-G compared to in EPA-I. However, CD86- and CD163-positive cell ratio was not significantly different between EPA-I and EPA-G. The average-sum F4/80 score of synovitis in EPA-G was significantly improved compared to in EPA-I. Conclusions EPA-incorporating gelatin hydrogels can prevent OA progression in vivo more effectively than single injection of EPA. Our results suggested that intra-articular administration of controlled-release EPA can be a new therapeutic approach for treating OA.
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