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

Abstract

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.

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Abbreviations

ANOVA:

Analysis of Variance

atRA:

All trans Retinoic Acid

ATII:

Alveolar type II cells

BAL:

Bronchoalveolar lavage

β-GP:

Beta-glycerophosphate

CCK-8:

Cell counting kit 8

COPD:

Chronic Obstructive Pulmonary Disease

ELISA:

Enzyme linked immunosorbent assay

HD:

High dose

hMSCs:

Human mesenchymal stem cells

IL:

Interleukin

LD:

Low dose

MC:

Methylcellulose

SD:

Standard deviation

SEM:

Standard error of mean

SLN:

Solid lipid nanoparticle

TEM:

Transmission electron microscopy

TNF:

Tumour necrosis factor

Z-ave:

Nanoparticle average size

ZP:

Zeta potential

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Correspondence to Helena M. Kelly.

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Chemical compounds studied in this article

all trans Retinoic Acid (atRA) (PubChem CID: 444795)

Appendix

Appendix

All trans Retinoic Acid Standard Curve

Fig. 11
figure11

Representative standard curve for all trans retinoic acid (atRA), as determined via HPLC.

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Payne, C.M., Burke, L.P., Cavanagh, B. et al. 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. Pharm Res 36, 50 (2019). https://doi.org/10.1007/s11095-019-2583-x

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KEY WORDS

  • all trans retinoic acid
  • chronic obstructive pulmonary disease
  • human mesenchymal stem cells
  • immunomodulatory
  • solid lipid nanoparticles