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Pharmaceutical Research

, 36:50 | Cite as

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

  • Christina M. Payne
  • Liam P. Burke
  • Brenton Cavanagh
  • Daniel O’Toole
  • Sally-Ann Cryan
  • Helena M. KellyEmail author
Research Paper

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.

KEY WORDS

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

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

Notes

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Authors and Affiliations

  1. 1.School of PharmacyRoyal College of Surgeons in IrelandDublin 2Ireland
  2. 2.Tissue Engineering Research Group, Department of AnatomyRoyal College of Surgeons in IrelandDublin 2Ireland
  3. 3.Discipline of Bacteriology, School of MedicineNational University of Ireland GalwayGalwayIreland
  4. 4.Cellular and Molecular Imaging CoreRoyal College of Surgeons in IrelandDublin 2Ireland
  5. 5.Discipline of Anaesthesia, School of MedicineNational University of Ireland GalwayGalwayIreland
  6. 6.Centre for Research in Medical Devices (CÚRAM)National University of Ireland GalwayGalwayIreland
  7. 7.Trinity Centre for BioengineeringTrinity College DublinDublin 2Ireland

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