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
Open accessAbstract
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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Human mesenchymal stem cells exposed to ATRA-loaded solid lipid nanoparticles significantly reduced IL-6 and IL-8 expression.
“human mesenchymal stem cells exposed to ATRA-loaded solid lipid nanoparticles significantly reduced IL-6 and IL-8 expression74.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [74]
Retinoids have been described as potent anti-inflammatory and protective in pathologies such as chronic obstructive pulmonary disease, rheumatoid arthritis, psoriasis, and inflammatory bowel disease.
“retinoids have been described as potent anti-inflammatory and therefore protective in pathologies such as chronic obstructive pulmonary disease74, rheumatoid arthritis122, psoriasis123, and inflammatory bowel disease124.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [74]
The advantages of RA-containing nanoparticles versus free RA were demonstrated by inhibiting expression of IL-6 and IL-8 in alveolar epithelial cells, but were not demonstrated in the induction of immune cell differentiation.
“The advantages of RA-containing nanoparticles versus free RA were demonstrated by inhibiting expression of IL-6 and IL-8 in alveolar epithelial cells74, but were not demonstrated in the induction of immune cell differentiation.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [74]
In general, RA formulations showed sustained intracellular RA delivery for a few days.
“In general, RA formulations showed sustained intracellular RA delivery for a few days58,74.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [74]
RA formulations with an average diameter of 130-250 nm and an entrapment efficiency of ATRA between 2.3 and 310 μg per mg of nanoparticle have been developed.
“RA formulations with an average diameter of 130–250 nm58,74 and an entrapment efficiency of ATRA between 2.3 and 310 μg124 per mg of nanoparticle have been developed.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [74]
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References 63 · Cited by 17
- Authors
- Payne, C. M., Burke, L. P., Cavanagh, B., O’Toole, D., Cryan, S.-A., & Kelly, H. M.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- Ollscoil na Gaillimhe – University of Galway (IE)
- Corresponding author
- Kelly, Helena M.
- ORCID
- Venue
- Pharmaceutical Research
- Published
- 2019-02-13
- Volume
- 36
- Issue
- 4
- Pages
- 50-50
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W2911930403
- Cited by
- 17
- References
- 63
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 3
- FWCI
- 1.06
- Type
- journal article
- Language
- en
- Open access
- green
- epubs.rcsi.ie
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (tdm)
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Royal College of Surgeons in Ireland (submittedVersion, cc-by-nc-sa)
- Figshare (submittedVersion, cc-by-nc-sa)
- Funders
- Science Foundation Ireland (13/IA/840)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- all-trans retinoic acid, solid lipid nanoparticles, human mesenchymal stem cells, chronic obstructive pulmonary disease, immunomodulation, A549 cells, interleukin-6, interleukin-8, sustained drug release, anti-inflammatory therapy
- MeSH terms
- A549 Cells, Anti-Inflammatory Agents, Cell Survival, Collagen, Drug Carriers, Glycerophosphates, Humans, Immunologic Factors, Interleukins, Lipids, Methylcellulose, Tretinoin, Signal Transduction, Hydrogels, Pulmonary Disease, Chronic Obstructive, Mesenchymal Stem Cell Transplantation, Nanoparticles, Immunomodulation
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