Jacob Eden Mariam, Borah Ankita, Pillai Sindhu C, Kumar D Sakthi
Bio Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, 2100 Kujirai, Kawagoe, Saitama 350-8585, Japan.
Polymers (Basel). 2021 Mar 11;13(6):862. doi: 10.3390/polym13060862.
The emergence of pH-sensitive nanoscale particles is beneficial due to their ability to only release cargo in a colonic pH environment, which helps to directly target inflamed tissues in inflammatory bowel disease (IBD). Hence, we have designed the formulation of pH-sensitive biodegradable garcinol (GAR)-loaded poly (lactic--glycolic acid) (PLGA) coated with Eudragit S100 (ES100) (GAR-PLGA-ES100 nanoparticles (NPs)) for reducing inflammation caused by proinflammatory cytokines. The GAR-PLGA-ES100 NPs were prepared using a solvent evaporation technique and characterized for shape and surface morphology. An in vitro drug release study revealed the release of the drug specifically from NPs at the colonic pH of 7.4. The in vitro cytotoxicity of the GAR-PLGA-ES100 NPs was also evaluated and found to be highly biocompatible with CACO-2 cells. These NPs were able to reduce lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity. Inhibition of the expression of pro-inflammatory cytokine TNF-α , chemokine interleukin (IL)-8 and the nuclear factor kappa light chain enhancer of activated B-cells (NF-κB) was observed after GAR-PLGA-ES100 NPs treatment. Therefore, our results support the idea that GAR-PLGA-ES100 NPs show substantial improvement after the release of the drug, specifically in colonic pH targeting and reduction in the activation of inflammation that leads to IBD, suggesting that GAR-PLGA-ES100 NPs are promising candidates for oral delivery to colonic inflamed tissue.
pH敏感纳米级颗粒的出现是有益的，因为它们能够仅在结肠pH环境中释放所载药物，这有助于直接靶向炎症性肠病（IBD）中的炎症组织。因此，我们设计了一种制剂，即载有pH敏感的可生物降解藤黄酸（GAR）的聚乳酸-乙醇酸共聚物（PLGA），并用Eudragit S100（ES100）包衣（GAR-PLGA-ES100纳米颗粒（NPs）），以减轻促炎细胞因子引起的炎症。采用溶剂蒸发技术制备了GAR-PLGA-ES100 NPs，并对其形状和表面形态进行了表征。体外药物释放研究表明，该药物在结肠pH值为7.4时从NPs中特异性释放。还评估了GAR-PLGA-ES100 NPs的体外细胞毒性，发现其与Caco-2细胞具有高度生物相容性。这些NPs能够降低乳酸脱氢酶（LDH）和髓过氧化物酶（MPO）的活性。在GAR-PLGA-ES100 NPs处理后，观察到促炎细胞因子TNF-α、趋化因子白细胞介素（IL）-8和活化B细胞的核因子κB轻链增强子（NF-κB）的表达受到抑制。因此，我们的结果支持这样的观点，即GAR-PLGA-ES100 NPs在药物释放后显示出显著改善，特别是在结肠pH靶向和减少导致IBD的炎症激活方面，这表明GAR-PLGA-ES100 NPs是口服递送至结肠炎症组织的有前途的候选药物。
