Regulation of inflammatory response of macrophages and induction of regulatory T cells by using retinoic acid-loaded nanostructured lipid carrier
Open accessAbstract
Immunomodulatory function of all-trans retinoic acid (ATRA) has been gathering much attention for the therapy of autoimmune diseases. ATRA is a chemically unstable molecule which requires proper formulation for targeted delivery. Here we examined nanostructured lipid carrier (NLC) for the formulation of ATRA. NLC is a representative nanoparticle formulation especially suited for oral delivery. We established the preparation procedures of ATRA-containing NLC (NLC-RA) which minimizes the degradation of ATRA during the preparation process. NLC-RA thus obtained was taken up by macrophages and induced anti-inflammatory response via suppressing NF-κB signaling as well as via enhancing the production of anti-inflammatory cytokines. Moreover, NLC-RA enhanced differentiation of naïve T cells to regulatory T cells in the co-culture system with dendritic cells. These results suggest that NLC-RA is a promising alternative therapy for the autoimmune diseases especially intestinal bowel disease.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
RA formulations are taken up by macrophages and induce anti-inflammatory responses by suppressing NF-kB signaling and increasing bone morphogenetic protein 2 signaling, as well as by enhancing the production of anti-inflammatory cytokines (e.g., IL-10).
“RA formulations are taken up by macrophages and induce anti-inflammatory responses by suppressing NF-kB signaling and increasing bone morphogenetic protein 2 signaling (pivotal for bone and cartilage development), as well as by enhancing the production of anti-inflammatory cytokines (e.g., IL-10)58,124.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [124]
RA formulations have the capacity to enhance the differentiation of naïve T cells to regulatory T cells.
“RA formulations have the capacity to enhance the differentiation of naïve T cells to regulatory T cells124.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [124]
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 [124]
Cites
Vitamin effects on the immune system: Vitamins A and D take centre stage
Mora, J. R., Iwata, M., & von Andrian, U. H. (2008) · Nature Reviews Immunology · doi:10.1038/nri2378 · Cited by 1,559 · see citing works
Macrophage death and defective inflammation resolution in atherosclerosis
Tabas, I. (2010) · Nature Reviews Immunology · doi:10.1038/nri2675 · Cited by 1,120 · see citing works
Nanostructured lipid carriers (NLC) in cosmetic dermal products☆
MULLER, R., Petersen, R., Hommoss, A., & Pardeike, J. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.04.012 · Cited by 702 · see citing works
Lipid Nanoparticles with a Solid Matrix (SLN®, NLC®, LDC®) for Oral Drug Delivery
Muchow, M., Maincent, P., & Müller, R. H. (2008) · Drug Development and Industrial Pharmacy · doi:10.1080/03639040802130061 · Cited by 394 · see citing works
Devaraj, S., Li, D., & Jialal, I. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118848 · Cited by 333 · see citing works
Plasticity of CD4+ FoxP3+ T cells
Zhou, X., Bailey-Bucktrout, S. L., Jeker, L. T., & Bluestone, J. A. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.05.007 · Cited by 317 · see citing works
Mielke, L. A., Jones, S. A., Raverdeau, M., Higgs, R., Stefanska, A., Groom, J. R., Misiak, A., Dungan, L. S., Sutton, C. E., Streubel, G., et al. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20121588 · Cited by 297 · see citing works
Retinoic Acid and Immune Homeostasis: A Balancing Act
Erkelens, M. N., & Mebius, R. E. (2017) · Trends in Immunology · doi:10.1016/j.it.2016.12.006 · Cited by 255 · see citing works
NF-κB as a Target for Modulating Inflammatory Responses
Gasparini, C., & Feldmann, M. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212803530763 · Cited by 225 · see citing works
Solubility of retinoids in water
Szuts, E. Z., & Harosi, F. I. (1991) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(91)90482-x · Cited by 223 · see citing works
Modulation of T Cell and Innate Immune Responses by Retinoic Acid
Raverdeau, M., & Mills, K. H. G. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1303245 · Cited by 222 · see citing works
Zhao, J., Lloyd, C. M., & Noble, A. (2012) · Mucosal Immunology · doi:10.1038/mi.2012.76 · Cited by 221 · see citing works
Bai, A., Lü, N., Guo, Y., Liu, Z., Jiang, C., & Peng, Z. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0109006 · Cited by 167 · see citing works
Retinoic acid in the immune system
Pino‐Lagos, K., Benson, M. J., & Noelle, R. J. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1443.017 · Cited by 138 · see citing works
Retinoic Acid Attenuates Rheumatoid Inflammation in Mice
Kwok, S., Park, M.-K., Cho, M., Oh, H., Park, E., Lee, D., Lee, J. J., Kim, H., & Park, S. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102706 · Cited by 99 · see citing works
Reifen, R. M., Nur, T., Zaiger, G., Urizky, R., Ghebermeskel, K., & Pines, M. (2002) · Journal of Nutrition · doi:10.1093/jn/132.9.2743 · Cited by 82 · see citing works
All-trans retinoic acid attenuates experimental colitis through inhibition of NF-κB signaling
Hong, K. M., Zhang, Y., Guo, Y., Xie, J., Wang, J., He, X., Lü, N., & Bai, A. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.06.011 · Cited by 78 · see citing works
Achkar, C. C., Bentel, J. M., Boylan, J. F., Scher, H. I., Gudas, L. J., & Miller, W. H. (1994) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08398-9 · Cited by 60 · see citing works
Modulation of lipopolysaccharide-mediated activation in rat Kupffer cells by antioxidants
Bellezzo, J. M., Leingang, K. A., Bulla, G. A., Britton, R. S., Bacon, B. R., & Fox, E. S. (1998) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(98)90075-0 · Cited by 54 · see citing works
Paradoxical Effects of All-Trans-Retinoic Acid on Lupus-Like Disease in the MRL/lpr Mouse Model
Liao, X., Ren, J., Wei, C.-H., Ross, A. C., Cecere, T. E., Jortner, B. S., Ahmed, S. A., & Luo, X. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118176 · Cited by 43 · see citing works
Vitamin A improve Th17 and Treg regulation in systemic lupus erythematosus
Handono, K., Firdausi, S. N., Pratama, M. Z., Endharti, A. T., & Kalim, H. (2016) · Clinical Rheumatology · doi:10.1007/s10067-016-3197-x · Cited by 42 · see citing works
Tan, X., Meltzer, N. M., & Lindenbaum, S. (1993) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/0731-7085(93)80074-b · Cited by 23 · see citing works
Sakamoto, H., Koya, T., Tsukioka, K., Shima, K., Watanabe, S., Kagamu, H., Kimura, Y., Sakagami, T., Hasegawa, T., Suzuki, E., et al. (2015) · International Archives of Allergy and Immunology · doi:10.1159/000437326 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Functional silk fibroin hydrogels: preparation, properties and applications
Zheng, H., & Zuo, B. (2020) · Journal of Materials Chemistry B · doi:10.1039/d0tb02099k · Cited by 376 · see citing works
Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine
Ferreira, R., Napoli, J., Enver, T., Bernardino, L., & Ferreira, L. (2020) · Nature Communications · doi:10.1038/s41467-020-18042-2 · Cited by 138 · see citing works
Cao, X., Wang, Y., Chen, H., Hu, J., & Cui, L. (2021) · Composites Part B Engineering · doi:10.1016/j.compositesb.2021.108934 · Cited by 63 · see citing works
Application of electrospun nanofibers in bone, cartilage and osteochondral tissue engineering
Ding, H., Cheng, Y., Niu, X., & Hu, Y. (2020) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2020.1849922 · Cited by 40 · see citing works
Novel chitosan/gelatin/oxidized cellulose sponges as absorbable hemostatic agents
Ranjbar, J., Koosha, M., Chi, H., Ghasemi, A., Zare, F., Abdollahifar, M., Darvishi, M., & Li, T. (2021) · Cellulose · doi:10.1007/s10570-021-03699-9 · Cited by 36 · see citing works
Liu, S., Zheng, Y., Wu, Z., Hu, J., & Liu, R. (2020) · Polymer · doi:10.1016/j.polymer.2020.123093 · Cited by 35 · see citing works
Ojah, N., Borah, R., Ahmed, G. A., Mandal, M., & Choudhury, A. J. (2020) · Progress in Biomaterials · doi:10.1007/s40204-020-00144-1 · Cited by 35 · see citing works
Nano Spray-Dried Drugs for Oral Administration: A Review
Öztürk, A. A., & Arpagaus, C. (2021) · Assay and Drug Development Technologies · doi:10.1089/adt.2021.053 · Cited by 32 · see citing works
Effect of retinoic acid on the neurovascular unit: A review
Pouso, M. R., & Cairrão, E. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.03.011 · Cited by 27 · see citing works
Kharaghani, D., Dutta, D., Ho, K. K. K., Zhang, K.-Q., Wei, K., Ren, X., Willcox, M. D. P., & Kim, I. S. (2020) · Cellulose · doi:10.1007/s10570-020-02999-w · Cited by 26 · see citing works
Retinoic acid in Parkinson's disease: Molecular insights, therapeutic advances, and future prospects
Pareek, A., Singhal, R., Pareek, A., Ghazi, T., Kapoor, D. U., Ratan, Y., Singh, A. K., Jain, V., & Chuturgoon, A. A. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.123010 · Cited by 21 · see citing works
Wang, T., Lin, C., Batalu, D., Zhang, L., Hu, J., & Lü, W. (2021) · Journal of Magnesium and Alloys · doi:10.1016/j.jma.2020.12.014 · Cited by 19 · see citing works
Lu, Y., Wang, J., & Zhang, C. (2021) · Journal of Rubber Research · doi:10.1007/s42464-020-00079-z · Cited by 14 · see citing works
Benchikh, L., Aouissi, T., Ferhat, Y. A., Chorfi, H., Abacha, I., Kebaili, M., Guessoum, M., Merzouki, A., Grohens, Y., Carraro, M., et al. (2024) · Polymer Bulletin · doi:10.1007/s00289-024-05225-w · Cited by 12 · see citing works
Targeting eosinophils in chronic respiratory diseases using nanotechnology-based drug delivery
Sharma, P., Dhanjal, D. S., Chopra, C., Tambuwala, M. M., Sohal, S. S., van der Spek, P. J., SHARMA, H. S., & Satija, S. (2022) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2022.110050 · Cited by 12 · see citing works
Diwu, W., Dong, X., Nasif, O., Alharbi, S. A., Zhao, J., & Li, W. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.631107 · Cited by 11 · see citing works
Kang, H., & Lee, S. (2023) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2023.108509 · Cited by 3 · see citing works
Experimental Study of Nanostructured Lipid Carrier in the Treatment of Immune Lupus Nephritis
Li, Y., & Qi, W. (2020) · Journal of Nanoscience and Nanotechnology · doi:10.1166/jnn.2021.18671 · Cited by 3 · see citing works
Sowmya, S., & Sangavi, R. (2025) · Journal of Indian Academy of Oral Medicine and Radiology · doi:10.4103/jiaomr.jiaomr_291_24 · Cited by 2 · see citing works
Potential Biodegradable Product from Dewatered Sludge
Marsilla, K. I. K., Alias, S. A., & Alias, N. F. (2023) · Green energy and technology · doi:10.1007/978-981-99-1083-0_13
- Authors
- Zai, K., Ishihara, N., Oguchi, H., Hirota, M., Kishimura, A., Mori, T., Hase, K., & Katayama, Y.
- Affiliations
- Kyushu University (JP)
- Keio University (JP)
- Corresponding author
- Mori, Takeshi
- ORCID
- Venue
- Journal of Biomaterials Science, Polymer Edition
- Publisher
- Informa UK Limited
- Published
- 2019-01-02
- Volume
- 30
- Issue
- 1
- Pages
- 1-11
- ISSN
- 0920-5063 (ISSN-L)
- 1568-5624
- OpenAlex
- W2810524929
- Cited by
- 20
- References
- 23
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 7
- FWCI
- 1.53
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- cc-by
- Locations
- Journal of Biomaterials Science Polymer Edition (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Figshare (cc-by)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Society for the Promotion of Science (18H04680, 17H04089, 17KT0055)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- all-trans retinoic acid, nanostructured lipid carriers, macrophages, regulatory T cells, NF-κB signaling, anti-inflammatory response, oral drug delivery, dendritic cells, T cell differentiation, autoimmune disease, intestinal inflammation, nanoparticle formulation
- MeSH terms
- RAW 264.7 Cells, Animals, Anti-Inflammatory Agents, Drug Carriers, Humans, Lipids, Macrophage Activation, Macrophages, Tretinoin, Coculture Techniques, T-Lymphocytes, Regulatory, Mice, Nanocapsules
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
