Evaluation of the Immunomodulatory Effects of All-Trans Retinoic Acid Solid Lipid Nanoparticles and Human Mesenchymal Stem Cells in an A549 Epithelial Cell Line Model.

Payne, Christina M.; Burke, Liam P.; Cavanagh, Brenton; O'Toole, Daniel; Cryan, Sally-Ann; Kelly, Helena M.

Purpose: 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). Methods: 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. Results: 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. Conclusion: 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.

HUMAN stem cells; MESENCHYMAL stem cells; EPITHELIAL cells; NANOPARTICLE toxicity; TRETINOIN; CELL lines

Pharmaceutical Research, 2019, Vol 36, Issue 4, pN.PAG

0724-8741

Academic Journal

10.1007/s11095-019-2583-x