{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:34:48Z","timestamp":1773873288712,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["DL57\/2016\/CP1361\/CT0006"],"award-info":[{"award-number":["DL57\/2016\/CP1361\/CT0006"]}]},{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["EXPL\/BTM-TEC\/0990\/2021"],"award-info":[{"award-number":["EXPL\/BTM-TEC\/0990\/2021"]}]},{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["UIDB\/04326\/2020"],"award-info":[{"award-number":["UIDB\/04326\/2020"]}]},{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["UIDP\/04326\/2020"],"award-info":[{"award-number":["UIDP\/04326\/2020"]}]},{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["LA\/P\/0101\/2020"],"award-info":[{"award-number":["LA\/P\/0101\/2020"]}]},{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["41\/ALG\/2020"],"award-info":[{"award-number":["41\/ALG\/2020"]}]},{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["072583"],"award-info":[{"award-number":["072583"]}]},{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["SFRH\/BD\/111824\/2015"],"award-info":[{"award-number":["SFRH\/BD\/111824\/2015"]}]},{"name":"Portuguese National Funds from FCT\u2014Foundation for Science and Technology","award":["PD\/BD\/137064\/2018"],"award-info":[{"award-number":["PD\/BD\/137064\/2018"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["DL57\/2016\/CP1361\/CT0006"],"award-info":[{"award-number":["DL57\/2016\/CP1361\/CT0006"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["EXPL\/BTM-TEC\/0990\/2021"],"award-info":[{"award-number":["EXPL\/BTM-TEC\/0990\/2021"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["UIDB\/04326\/2020"],"award-info":[{"award-number":["UIDB\/04326\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["UIDP\/04326\/2020"],"award-info":[{"award-number":["UIDP\/04326\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["LA\/P\/0101\/2020"],"award-info":[{"award-number":["LA\/P\/0101\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["41\/ALG\/2020"],"award-info":[{"award-number":["41\/ALG\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["072583"],"award-info":[{"award-number":["072583"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["SFRH\/BD\/111824\/2015"],"award-info":[{"award-number":["SFRH\/BD\/111824\/2015"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["PD\/BD\/137064\/2018"],"award-info":[{"award-number":["PD\/BD\/137064\/2018"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["DL57\/2016\/CP1361\/CT0006"],"award-info":[{"award-number":["DL57\/2016\/CP1361\/CT0006"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["EXPL\/BTM-TEC\/0990\/2021"],"award-info":[{"award-number":["EXPL\/BTM-TEC\/0990\/2021"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["UIDB\/04326\/2020"],"award-info":[{"award-number":["UIDB\/04326\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["UIDP\/04326\/2020"],"award-info":[{"award-number":["UIDP\/04326\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["LA\/P\/0101\/2020"],"award-info":[{"award-number":["LA\/P\/0101\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["41\/ALG\/2020"],"award-info":[{"award-number":["41\/ALG\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["072583"],"award-info":[{"award-number":["072583"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["SFRH\/BD\/111824\/2015"],"award-info":[{"award-number":["SFRH\/BD\/111824\/2015"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["PD\/BD\/137064\/2018"],"award-info":[{"award-number":["PD\/BD\/137064\/2018"]}]},{"name":"NUTRISAFE","award":["DL57\/2016\/CP1361\/CT0006"],"award-info":[{"award-number":["DL57\/2016\/CP1361\/CT0006"]}]},{"name":"NUTRISAFE","award":["EXPL\/BTM-TEC\/0990\/2021"],"award-info":[{"award-number":["EXPL\/BTM-TEC\/0990\/2021"]}]},{"name":"NUTRISAFE","award":["UIDB\/04326\/2020"],"award-info":[{"award-number":["UIDB\/04326\/2020"]}]},{"name":"NUTRISAFE","award":["UIDP\/04326\/2020"],"award-info":[{"award-number":["UIDP\/04326\/2020"]}]},{"name":"NUTRISAFE","award":["LA\/P\/0101\/2020"],"award-info":[{"award-number":["LA\/P\/0101\/2020"]}]},{"name":"NUTRISAFE","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"NUTRISAFE","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"NUTRISAFE","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"NUTRISAFE","award":["41\/ALG\/2020"],"award-info":[{"award-number":["41\/ALG\/2020"]}]},{"name":"NUTRISAFE","award":["072583"],"award-info":[{"award-number":["072583"]}]},{"name":"NUTRISAFE","award":["SFRH\/BD\/111824\/2015"],"award-info":[{"award-number":["SFRH\/BD\/111824\/2015"]}]},{"name":"NUTRISAFE","award":["PD\/BD\/137064\/2018"],"award-info":[{"award-number":["PD\/BD\/137064\/2018"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["DL57\/2016\/CP1361\/CT0006"],"award-info":[{"award-number":["DL57\/2016\/CP1361\/CT0006"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["EXPL\/BTM-TEC\/0990\/2021"],"award-info":[{"award-number":["EXPL\/BTM-TEC\/0990\/2021"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["UIDB\/04326\/2020"],"award-info":[{"award-number":["UIDB\/04326\/2020"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["UIDP\/04326\/2020"],"award-info":[{"award-number":["UIDP\/04326\/2020"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["LA\/P\/0101\/2020"],"award-info":[{"award-number":["LA\/P\/0101\/2020"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["41\/ALG\/2020"],"award-info":[{"award-number":["41\/ALG\/2020"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["072583"],"award-info":[{"award-number":["072583"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["SFRH\/BD\/111824\/2015"],"award-info":[{"award-number":["SFRH\/BD\/111824\/2015"]}]},{"name":"Portuguese Science and Technology Foundation (FCT)","award":["PD\/BD\/137064\/2018"],"award-info":[{"award-number":["PD\/BD\/137064\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic inflammation is a major driver of chronic inflammatory diseases (CIDs), with a tremendous impact worldwide. Besides its function as a pathological calcification inhibitor, vitamin K-dependent protein Gla-rich protein (GRP) was shown to act as an anti-inflammatory agent independently of its gamma-carboxylation status. Although GRP\u2019s therapeutic potential has been highlighted, its low solubility at physiological pH still constitutes a major challenge for its biomedical application. In this work, we produced fluorescein-labeled chitosan-tripolyphosphate nanoparticles containing non-carboxylated GRP (ucGRP) (FCNG) via ionotropic gelation, increasing its bioavailability, stability, and anti-inflammatory potential. The results indicate the nanosized nature of FCNG with PDI and a zeta potential suitable for biomedical applications. FCNG\u2019s anti-inflammatory activity was studied in macrophage-differentiated THP1 cells, and in primary vascular smooth muscle cells and chondrocytes, inflamed with LPS, TNF\u03b1 and IL-1\u03b2, respectively. In all these in vitro human cell systems, FCNG treatments resulted in increased intra and extracellular GRP levels, and decreased pro-inflammatory responses of target cells, by decreasing pro-inflammatory cytokines and inflammation mediators. These results suggest the retained anti-inflammatory bioactivity of ucGRP in FCNG, strengthening the potential use of ucGRP as an anti-inflammatory agent with a wide spectrum of application, and opening up perspectives for its therapeutic application in CIDs.<\/jats:p>","DOI":"10.3390\/ijms23094813","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T13:40:57Z","timestamp":1651066857000},"page":"4813","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation"],"prefix":"10.3390","volume":"23","author":[{"given":"Carla S. B.","family":"Viegas","sequence":"first","affiliation":[{"name":"Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"given":"Nuna","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3048-8820","authenticated-orcid":false,"given":"Joana","family":"Carreira","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6447-0242","authenticated-orcid":false,"given":"Jorge F.","family":"Pontes","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2613-4838","authenticated-orcid":false,"given":"Anjos L.","family":"Macedo","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Departamento de Qu\u00edmica, and Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal"}]},{"given":"Maur\u00edcia","family":"Vinhas","sequence":"additional","affiliation":[{"name":"Algarve Biomedical Center Research Institute (ABC-RI), Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"given":"Ana S.","family":"Moreira","sequence":"additional","affiliation":[{"name":"iBET\u2014Instituto de Biologia Experimental e Tecnol\u00f3gica, 2780-157 Oeiras, Portugal"},{"name":"ITQB\u2014Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"}]},{"given":"Tiago Q.","family":"Faria","sequence":"additional","affiliation":[{"name":"iBET\u2014Instituto de Biologia Experimental e Tecnol\u00f3gica, 2780-157 Oeiras, Portugal"},{"name":"ITQB\u2014Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2136-1396","authenticated-orcid":false,"given":"Ana","family":"Grenha","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"given":"Ant\u00f3nio A.","family":"de Matos","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar Egas Moniz, Egas Moniz-Cooperativa de Ensino Superior CRL, 2829-511 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7867-6957","authenticated-orcid":false,"given":"Leon","family":"Schurgers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cardiovascular Research Institute, Maastricht University, 6229 HX Maastricht, The Netherlands"}]},{"given":"Cees","family":"Vermeer","sequence":"additional","affiliation":[{"name":"Cardiovscular Research Institute CARIM, Maastricht University, 6229 HX Maastricht, The Netherlands"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5145-4753","authenticated-orcid":false,"given":"Dina C.","family":"Simes","sequence":"additional","affiliation":[{"name":"Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"ref_1","unstructured":"Pahwa, R., Goyal, A., Bansal, P., and Jialal, I. (2021). Chronic Inflammation, StatPearls Publishing."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2018","journal-title":"Oncotarget"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"143","DOI":"10.14336\/AD.2017.0306","article-title":"Comprehensive Review of Non-Steroidal Anti-Inflammatory Drug Use in The Elderly","volume":"9","author":"Wongrakpanich","year":"2018","journal-title":"Aging Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Viegas, C.S.B., Costa, R.M., Santos, L., Videira, P.A., Silva, Z., Ara\u00fajo, N., Macedo, A.L., Matos, A.P., Vermeer, C., and Simes, D.C. (2017). Gla-rich protein function as an anti-inflammatory agent in monocytes\/macrophages: Implications for calcification-related chronic inflammatory diseases. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177829"},{"key":"ref_6","unstructured":"Chatterjee, S., Jungraithmayr, W., and Bagchi, D. (2018). Chapter 15\u2014Inflammation and Calcification in the Vascular Tree; Insights into Atherosclerosis. Immunity and Inflammation in Health and Disease, Academic Press."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"36655","DOI":"10.1074\/jbc.M802761200","article-title":"Gla-rich protein (GRP), a new vitamin K-dependent protein identified from sturgeon cartilage and highly conserved in vertebrates","volume":"283","author":"Viegas","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7082","DOI":"10.1074\/jbc.M702792200","article-title":"Ucma, a novel secreted cartilage-specific protein with implications in osteogenesis","volume":"283","author":"Dietz","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1007\/s00018-015-2033-9","article-title":"Gla-rich protein is involved in the cross-talk between calcification and inflammation in osteoarthritis","volume":"73","author":"Cavaco","year":"2016","journal-title":"Cell Mol. Life Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1161\/ATVBAHA.114.304823","article-title":"Gla-rich protein acts as a calcification inhibitor in the human cardiovascular system","volume":"35","author":"Viegas","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1161\/ATVBAHA.117.310578","article-title":"Chronic Kidney Disease Circulating Calciprotein Particles and Extracellular Vesicles Promote Vascular Calcification: A Role for GRP (Gla-Rich Protein)","volume":"38","author":"Viegas","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1002\/art.40042","article-title":"A Dual Role of Upper Zone of Growth Plate and Cartilage Matrix-Associated Protein in Human and Mouse Osteoarthritic Cartilage: Inhibition of Aggrecanases and Promotion of Bone Turnover","volume":"69","author":"Stock","year":"2017","journal-title":"Arthritis Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13075-018-1583-2","article-title":"Upper zone of growth plate and cartilage matrix associated protein protects cartilage during inflammatory arthritis","volume":"20","author":"Seuffert","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4961","DOI":"10.1038\/s41598-018-23353-y","article-title":"Ucma\/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling","volume":"8","author":"Willems","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Silva, A.P., Viegas, C.S., Mendes, F., Macedo, A., Guilherme, P., Tavares, N., Dias, C., Rato, F., Santos, N., and Fa\u00edsca, M. (2020). Gla-Rich Protein (GRP) as an Early and Novel Marker of Vascular Calcification and Kidney Dysfunction in Diabetic Patients with CKD: A Pilot Cross-Sectional Study. J. Clin. Med., 9.","DOI":"10.3390\/jcm9030635"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Silva, A.P., Viegas, C.S.B., Guilherme, P., Tavares, N., Dias, C., Rato, F., Santos, N., Fa\u00edsca, M., de Almeida, E., and Neves, P.L. (2022). Gla-Rich Protein, Magnesium and Phosphate Associate with Mitral and Aortic Valves Calcification in Diabetic Patients with Moderate CKD. Diagnostics, 12.","DOI":"10.3390\/diagnostics12020496"},{"key":"ref_17","first-page":"265","article-title":"Nanoencapsulation for drug delivery","volume":"13","author":"Kumari","year":"2014","journal-title":"EXCLI J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3389\/fphys.2019.00516","article-title":"Biological Effects and Applications of Chitosan and Chito-Oligosaccharides","volume":"10","author":"Guan","year":"2019","journal-title":"Front Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mohammed, M.A., Syeda, J.T.M., Wasan, K.M., and Wasan, E.K. (2017). An Overview of Chitosan Nanoparticles and Its Application in Non-Parenteral Drug Delivery. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9040053"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.colsurfb.2007.04.009","article-title":"Chitosan nanoparticle as protein delivery carrier--systematic examination of fabrication conditions for efficient loading and release","volume":"59","author":"Gan","year":"2007","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2000312","DOI":"10.1002\/mabi.202000312","article-title":"Biomedical and Pharmacological Uses of Fluorescein Isothiocyanate Chitosan-Based Nanocarriers","volume":"21","author":"Caprifico","year":"2021","journal-title":"Macromol. Biosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.carbpol.2017.07.058","article-title":"Preparation and biological activity studies of resveratrol loaded ionically cross-linked chitosan-TPP nanoparticles","volume":"175","author":"Wu","year":"2017","journal-title":"Carbohydr. Polym."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3390\/biom5010003","article-title":"Biodegradable chitosan nanoparticle coatings on titanium for the delivery of BMP-2","volume":"5","author":"Poth","year":"2015","journal-title":"Biomolecules"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.ejps.2005.04.009","article-title":"Microencapsulated chitosan nanoparticles for lung protein delivery","volume":"25","author":"Grenha","year":"2005","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1023\/B:PHAM.0000026432.75781.cb","article-title":"Chitosan nanoparticles as new ocular drug delivery systems: In vitro stability, in vivo fate, and cellular toxicity","volume":"21","author":"Diebold","year":"2004","journal-title":"Pharm Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1023\/A:1020404615898","article-title":"Uptake of FITC-chitosan nanoparticles by A549 cells","volume":"19","author":"Huang","year":"2002","journal-title":"Pharm. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4695","DOI":"10.1038\/s41598-018-23064-4","article-title":"Parameters influencing the size of chitosan-TPP nano- and microparticles","volume":"8","author":"Sreekumar","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.colsurfb.2005.06.001","article-title":"Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery","volume":"44","author":"Gan","year":"2005","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nrrheum.2015.158","article-title":"Does lipopolysaccharide-mediated inflammation have a role in OA?","volume":"12","author":"Huang","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1042\/CS20080196","article-title":"Role of TNF-alpha in vascular dysfunction","volume":"116","author":"Zhang","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.atherosclerosis.2016.05.044","article-title":"Calcification of vascular smooth muscle cells is induced by secondary calciprotein particles and enhanced by tumor necrosis factor-\u03b1","volume":"251","author":"Aghagolzadeh","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"934","DOI":"10.12688\/f1000research.18831.1","article-title":"IL-1 in osteoarthritis: Time for a critical review of the literature","volume":"21","author":"Vincent","year":"2019","journal-title":"F1000Research"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/(SICI)1097-4628(19970103)63:1<125::AID-APP13>3.0.CO;2-4","article-title":"Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers","volume":"63","author":"Calvo","year":"1997","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.carbpol.2012.03.010","article-title":"Chitosan\/carrageenan nanoparticles: Effect of cross-linking with tripolyphosphate and charge ratios","volume":"89","author":"Rodrigues","year":"2012","journal-title":"Carbohydr. Polym."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.ijbiomac.2018.01.023","article-title":"Chitosan\/sodium tripolyphosphate nanoparticles as efficient vehicles for antioxidant peptidic fraction from common kilka","volume":"111","author":"Hosseini","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.colsurfa.2015.04.006","article-title":"Preparation of chitosan\u2013TPP nanoparticles using microengineered membranes\u2014Effect of parameters and encapsulation of tacrine","volume":"482","author":"Hassani","year":"2015","journal-title":"Colloids Surf. Physicochem. Eng. Asp."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3390\/jfb6010033","article-title":"Anticancer and anti-inflammatory properties of chitin and chitosan oligosaccharides","volume":"6","author":"Azuma","year":"2015","journal-title":"J. Funct. Biomater."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1081\/IPH-200026887","article-title":"Inhibitory effect of water-soluble chitosan on TNF-alpha and IL-8 secretion from HMC-1 cells","volume":"26","author":"Kim","year":"2004","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1038\/jid.2012.399","article-title":"Antimicrobial and anti-inflammatory activity of chitosan-alginate nanoparticles: A targeted therapy for cutaneous pathogens","volume":"133","author":"Friedman","year":"2013","journal-title":"J. Invest. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Jhundoo, H.D., Siefen, T., Liang, A., Schmidt, C., Lokhnauth, J., B\u00e9duneau, A., Pellequer, Y., Larsen, C.C., and Lamprecht, A. (2020). Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12111038"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.ejps.2017.11.020","article-title":"Novel controlled ionic gelation strategy for chitosan nanoparticles preparation using TPP-\u03b2-CD inclusion complex","volume":"112","author":"Pant","year":"2018","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6383","DOI":"10.2147\/IJN.S142060","article-title":"Intracellular disposition of chitosan nanoparticles in macrophages: Intracellular uptake, exocytosis, and intercellular transport","volume":"12","author":"Jiang","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.addr.2009.09.004","article-title":"Biodegradation, biodistribution and toxicity of chitosan","volume":"62","author":"Kean","year":"2010","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"340216","DOI":"10.1155\/2014\/340216","article-title":"Gla-rich protein is a potential new vitamin K target in cancer: Evidences for a direct GRP-mineral interaction","volume":"2014","author":"Viegas","year":"2014","journal-title":"Biomed Res. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1097\/01.ASN.0000141960.01035.28","article-title":"Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: A potential mechanism for accelerated vascular calcification in ESRD","volume":"15","author":"Reynolds","year":"2004","journal-title":"J. Am. Soc. Nephrol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/4813\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:01:53Z","timestamp":1760137313000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/9\/4813"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,27]]},"references-count":45,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["ijms23094813"],"URL":"https:\/\/doi.org\/10.3390\/ijms23094813","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,27]]}}}