Dexamethasone Acetate-Loaded PLGA Nanospheres Targeting Liver Macrophages
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
CZ.02.01.01/00/22_008/0004607
New Technologies for Translational Research in Pharmaceutical Sciences/NETPHARM, co-funded by the European Union
Project No
Long Term Organization Development Plan 1011 Healthcare Challenges of WMD II of the Military Faculty of Medicine, Hradec Kralove, University of Defence, Czech Republic
DZRO-FVZ22-ZHN II
Long Term Organization Development Plan 1011 Healthcare Challenges of WMD II of the Military Faculty of Medicine, Hradec Kralove, University of Defence, Czech Republic
SVV 260 661
Ministerstvo Školství, Mládeže a Tělovýchovy
PubMed
39611304
PubMed Central
PMC11827543
DOI
10.1002/mabi.202400411
Knihovny.cz E-zdroje
- Klíčová slova
- PLGA nanospheres, biodegradable nanoparticles, glucocorticoids, liver inflammation, macrophages,
- MeSH
- antiflogistika farmakologie chemie MeSH
- dexamethason * farmakologie chemie analogy a deriváty MeSH
- játra * účinky léků metabolismus MeSH
- kopolymer kyseliny glykolové a mléčné * chemie MeSH
- makrofágy * účinky léků metabolismus MeSH
- myši MeSH
- nanokuličky * chemie MeSH
- nosiče léků chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika MeSH
- dexamethason * MeSH
- dexamethasone acetate MeSH Prohlížeč
- kopolymer kyseliny glykolové a mléčné * MeSH
- nosiče léků MeSH
Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.
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Gasmi B., Kleiner D. E., Clin. Liver Dis. 2020, 24, 61. PubMed PMC
Gassler N., Press A., Rauchfuß F., Theis B., Kaemmerer E., AME. Med. J. 2022, 7.
Wen Y., Lambrecht J., Ju C., Tacke F., Cell. Mol. Immunol. 2021, 18, 45. PubMed PMC
Diaz‐Jimenez D., Kolb J. P., Cidlowski J. A., Front. Immunol. 2021, 12. PubMed PMC
Patel U., Rajasingh S., Samanta S., Cao T., Dawn B., Rajasingh J., Drug Discov. Today 2017, 22, 186. PubMed PMC
van der Heide D., Weiskirchen R., Bansal R., Front. Immunol. 2019, 10. PubMed PMC
Murray P. J., Annu. Rev. Physiol. 2017, 79, 541. PubMed
Greulich F., Hemmer M. C., Rollins D. A., Rogatsky I., Uhlenhaut N. H., Steroids 2016, 114, 7. PubMed PMC
Kleiman A., Hübner S., Parkitna J. M. R., Neumann A., Hofer S., Weigand M. A., Bauer M., Schmid W., Schütz G., Libert C., Reichardt H. M., Tuckermann J. P., FASEB. J. 2012, 26, 722. PubMed
Rhen T., Cidlowski J. A., N. Engl. J. Med. 2005, 353, 1711. PubMed
Præstholm S. M., Correia C. M., Grøntved L., Front. Endocrinol. (Lausanne) 2020, 11. PubMed PMC
Vegiopoulos A., Herzig S., Mol Cell. Endocrinol. 2007, 275, 43. PubMed
Tessier B., Tsapis N., Fattal E., Moine L., J. Controlled Release 2023, 358, 273. PubMed
Tammam S. N., Azzazy H. M. E., Lamprecht A., J. Biomed. Nanotechnol. 2014, 10, 555. PubMed
Boltnarova B., Kubackova J., Skoda J., Stefela A., Smekalova M., Svacinova P., Pavkova I., Dittrich M., Scherman D., Zbytovska J., Pavek P., Holas O., Nanomaterials 2021, 11, 749. PubMed PMC
Danhier F., Ansorena E., Silva J. M., Coco R., Le Breton A., Préat V., J. Controlled Release 2012, 161, 505. PubMed
Parente L., BMC. Pharmacol. Toxicol. 2017, 18, 1. PubMed PMC
Gómez‐Gaete C., Tsapis N., Besnard M., Bochot A., Fattal E., Int. J. Pharm. 2007, 331, 153. PubMed
Espinosa‐Cano E., Aguilar M. R., Portilla Y., Barber D. F., Román J. S., Pharmaceutics 2020, 12, 723. PubMed PMC
Espinosa‐Cano E., Aguilar M. R., Portilla Y., Barber D. F., San Román J., Macromol. Biosci. 2020, 20, 2000002. PubMed
Gómez‐Gaete C., Fattal E., Silva L., Besnard M., Tsapis N., J. Controlled Release 2008, 128, 41. PubMed
Colino C. I., Lanao J. M., Gutierrez‐Millan C., Front Immunol 2020, 11, 218. PubMed PMC
Béguin E. P., Przeradzka M. A., Janssen E. F. J., Meems H., Sedek M., van der Zwaan C., Mertens K., van den Biggelaar M., Meijer A. B., Mourik M. J., Haematologica 2020, 105, e133. PubMed PMC
Lunov O., Syrovets T., Loos C., Beil J., Delacher M., Tron K., Nienhaus G. U., Musyanovych A., Mailänder V., Landfester K., Simmet T., ACS Nano 2011, 5, 1657. PubMed
Wachowiak S., Danede F., Willart J. F., Siepmann F., Siepmann J., Hamoudi M., J. Drug Deliv. Sci. Technol. 2023, 86, 104648.
Medlock Kakaley E., Cardon M. C., Gray L. E., Hartig P. C., Wilson V. S., Toxicol. Sci. 2019, 168, 252. PubMed PMC
Cronin J., Kennedy U., McCoy S., an Fhailí S. N., Crispino‐O'Connell G., Hayden J., Wakai A., Walsh S., O'Sullivan R., Trials 2012, 13, 593. PubMed PMC
Zheng X. F., Hong Y. X., Feng G. J., Zhang G. F., Rogers H., Lewis M. A. O., Williams D. W., Xia Z. F., Song B., Wei X. Q., PLoS One 2013, 8. PubMed PMC
Kou L., Huang H., Tang Y., Sun M., Li Y., Wu J., Zheng S., Zhao X., Chen D., Luo Z., Zhang X., Yao Q., Chen R., J. Controlled Release 2022, 347, 237. PubMed
Borges Da Silva H., Fonseca R., Pereira R. M., Cassado A. A., Álvarez J. M., D'Império Lima M. R., Front. Immunol. 2015, 6. PubMed PMC
Bartneck M., Peters F. M., Warzecha K. T., Bienert M., van Bloois L., Trautwein C., Lammers T., Tacke F., Nanomedicine 2014, 10, 1209. PubMed
Andrew S. M., Titus J. A., Zumstein L., Curr. Protoc. Cell. Biol. 1999, 4. PubMed
Weischenfeldt J., Porse B., Cold. Spring. Harb. Protoc. 2008, 3.
Meng F., Lowell C. A., J. Exp. Med. 1997, 185, 1661. PubMed PMC
Nehmé A., Edelman J., Invest. Ophthalmol. Visual Sci. 2008, 49, 2030. PubMed
Franchimont D., Louis E., Dewe W., Martens H., Vrindts‐Gevaert Y., De Groote D., Belaiche J., Geenen V., Regul. Pept. 1998, 73, 59. PubMed
