School of Pharmacy, Royal College of Surgeons in Ireland, Ardilaun House Block B, 111 St Stephen's Green, Dublin 2, Ireland.
Tissue Engineering Research Group, Department of Anatomy, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
Pharm Res. 2019 Feb 13;36(4):50. doi: 10.1007/s11095-019-2583-x.
To investigate two potential strategies aimed at targeting the inflammatory pathogenesis of COPD: a small molecule, all trans retinoic acid (atRA) and human mesenchymal stem cells (hMSCs).
atRA was formulated into solid lipid nanoparticles (SLNs) via the emulsification-ultrasonication method, and these SLNs were characterised physicochemically. Assessment of the immunomodulatory effects of atRA-SLNs on A549 cells in vitro was determined using ELISA. hMSCs were suspended in a previously developed methylcellulose, collagen and beta-glycerophosphate hydrogel prior to investigating their immunomodulatory effects in vitro.
SLNs provided significant encapsulation of atRA and also sustained its release over 72 h. A549 cells were viable following the addition of atRA SLNs and showed a reduction in IL-6 and IL-8 levels. A549 cells also remained viable following addition of the hMSC/hydrogel formulation - however, this formulation resulted in increased levels of IL-6 and IL-8, indicating a potentially pro-inflammatory effect.
Both atRA SLNs and hMSCs show potential for modulating the environment in inflammatory disease, though through different mechanisms and leading to different outcomes - despite both being explored as strategies for use in inflammatory disease. atRA shows promise by acting in a directly anti-inflammatory manner, whereas further research into the exact mechanisms and behaviours of hMSCs in inflammatory diseases is required.
研究两种针对 COPD 炎症发病机制的潜在策略：全反式视黄酸（atRA）和人骨髓间充质干细胞（hMSC）。
采用乳化-超声法将 atRA 制成固体脂质纳米粒（SLN），并对其理化性质进行了表征。采用 ELISA 法测定 atRA-SLN 对体外 A549 细胞的免疫调节作用。将 hMSC 悬浮于先前开发的甲基纤维素、胶原和β-甘油磷酸盐水凝胶中，然后在体外研究其免疫调节作用。
SLN 显著包裹了 atRA，并且在 72 小时内持续释放。加入 atRA SLN 后 A549 细胞仍存活，并降低了 IL-6 和 IL-8 水平。加入 hMSC/水凝胶制剂后 A549 细胞也仍存活，但该制剂导致 IL-6 和 IL-8 水平升高，表明其具有潜在的促炎作用。
atRA SLN 和 hMSC 都显示出调节炎症性疾病环境的潜力，尽管其机制不同，结果也不同——尽管两者都被探索作为炎症性疾病的治疗策略。atRA 通过直接抗炎作用显示出良好的应用前景，而需要进一步研究 hMSC 在炎症性疾病中的确切机制和行为。
