{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:02:55Z","timestamp":1792699375564,"version":"4.5.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T00:00:00Z","timestamp":1672617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T00:00:00Z","timestamp":1672617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK2375"],"award-info":[{"award-number":["GRK2375"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011199","name":"FP7 Ideas: European Research Council","doi-asserted-by":"publisher","award":["Consolidator Grant 864121"],"award-info":[{"award-number":["Consolidator Grant 864121"]}],"id":[{"id":"10.13039\/100011199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007210","name":"RWTH Aachen University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007210","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drug Deliv. and Transl. Res."],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite the introduction of multiple new drugs and combination therapies, conventional dexamethasone remains a cornerstone in the treatment of multiple myeloma (MM). Its application is, however, limited by frequent adverse effects of which the increased infection rate may have the strongest clinical impact. The efficacy-safety ratio of dexamethasone in MM may be increased by encapsulation in long-circulating PEG-liposomes, thereby both enhancing drug delivery to MM lesions and reducing systemic corticosteroid exposure. We evaluated the preliminary safety and feasibility of a single intravenous (i.v.) infusion of pegylated liposomal dexamethasone phosphate (Dex-PL) in heavily pretreated relapsing or progressive symptomatic MM patients within a phase I open-label non-comparative interventional trial at two dose levels. In the 7 patients that were enrolled (prior to having to close the study prematurely due to slow recruitment), Dex-PL was found to be well tolerated and, as compared to conventional dexamethasone, no new or unexpected adverse events were detected. Pharmacokinetic analysis showed high and persisting concentrations of dexamethasone in the circulation for over a week after i.v. administration, likely caused by the long-circulation half-life of the liposomes that retain dexamethasone as the inactive phosphate prodrug form, something which could significantly limit systemic exposure to the active parent drug. Thus, despite the limitations of this small first-in-man trial, Dex-PL seems safe and well tolerated without severe side effects. Follow-up studies are needed to confirm this in a larger patient cohort and to evaluate if i.v. Dex-PL can provide a safer and more efficacious dexamethasone treatment option for MM.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s13346-022-01268-6","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T14:03:16Z","timestamp":1672668196000},"page":"915-923","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A phase I first-in-man study to investigate the pharmacokinetics and safety of liposomal dexamethasone in patients with progressive multiple myeloma"],"prefix":"10.1007","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1360-0112","authenticated-orcid":false,"given":"Josbert","family":"Metselaar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Twan","family":"Lammers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelie","family":"Boquoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Fenk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Testaquadra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirle","family":"Schemionek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Kiessling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Isfort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Wilop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Crysandt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,2]]},"reference":[{"issue":"11","key":"1268_CR1","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1056\/NEJMra1011442","volume":"364","author":"A Palumbo","year":"2011","unstructured":"Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046\u201360.","journal-title":"N Engl J Med"},{"issue":"3","key":"1268_CR2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/nrclinonc.2012.15","volume":"9","author":"A Mahindra","year":"2012","unstructured":"Mahindra A, et al. Latest advances and current challenges in the treatment of multiple myeloma. Nat Rev Clin Oncol. 2012;9(3):135\u201343.","journal-title":"Nat Rev Clin Oncol"},{"issue":"3","key":"1268_CR3","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/leu.2013.350","volume":"28","author":"EM Ocio","year":"2014","unstructured":"Ocio EM, et al. New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG). Leukemia. 2014;28(3):525\u201342.","journal-title":"Leukemia"},{"issue":"4","key":"1268_CR4","doi-asserted-by":"publisher","first-page":"278","DOI":"10.3816\/CLM.2009.n.056","volume":"9","author":"RA Kyle","year":"2009","unstructured":"Kyle RA, Rajkumar SV. Treatment of multiple myeloma: a comprehensive review. Clin Lymphoma Myeloma. 2009;9(4):278\u201388.","journal-title":"Clin Lymphoma Myeloma"},{"issue":"6","key":"1268_CR5","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1200\/JCO.2013.48.7934","volume":"32","author":"A Palumbo","year":"2014","unstructured":"Palumbo A, et al. International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation. J Clin Oncol. 2014;32(6):587\u2013600.","journal-title":"J Clin Oncol"},{"key":"1268_CR6","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.3389\/fonc.2020.01243","volume":"10","author":"LG Rodr\u00edguez-Lobato","year":"2020","unstructured":"Rodr\u00edguez-Lobato LG, et al. G CAR T-cells in multiple myeloma: state of the art and future directions. Front Oncol. 2020;10:1243.","journal-title":"Front Oncol"},{"issue":"2","key":"1268_CR7","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/leu.2017.329","volume":"32","author":"CS Chim","year":"2018","unstructured":"Chim CS, et al. Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond. Leukemia. 2018;32(2):252\u201362.","journal-title":"Leukemia"},{"issue":"6","key":"1268_CR8","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/sj.bmt.1704633","volume":"34","author":"S Kumar","year":"2004","unstructured":"Kumar S, et al. Single agent dexamethasone for pre-stem cell transplant induction therapy for multiple myeloma. Bone Marrow Transplant. 2004;34(6):485\u201390.","journal-title":"Bone Marrow Transplant"},{"issue":"4","key":"1268_CR9","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1111\/j.1600-0609.2008.01121.x","volume":"81","author":"M von Lilienfeld-Toal","year":"2008","unstructured":"von Lilienfeld-Toal M, et al. A systematic review of phase II trials of thalidomide\/dexamethasone combination therapy in patients with relapsed or refractory multiple myeloma. Eur J Haematol. 2008;81(4):247\u201352.","journal-title":"Eur J Haematol"},{"issue":"2","key":"1268_CR10","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.exphem.2012.10.002","volume":"41","author":"K Salem","year":"2013","unstructured":"Salem K, et al. Combination chemotherapy increases cytotoxicity of multiple myeloma cells by modification of nuclear factor (NF)-kappaB activity. Exp Hematol. 2013;41(2):209\u201318.","journal-title":"Exp Hematol"},{"issue":"3","key":"1268_CR11","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1002\/ajh.2830360303","volume":"36","author":"WR Friedenberg","year":"1991","unstructured":"Friedenberg WR, et al. High-dose dexamethasone for refractory or relapsing multiple myeloma. Am J Hematol. 1991;36(3):171\u20135.","journal-title":"Am J Hematol"},{"issue":"10192","key":"1268_CR12","doi-asserted-by":"publisher","first-page":"31240","DOI":"10.1016\/S0140-6736(19)31240-1","volume":"394","author":"P Moreau","year":"2019","unstructured":"Moreau P, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394(10192):31240\u20131.","journal-title":"Lancet"},{"issue":"1","key":"1268_CR13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S1470-2045(09)70284-0","volume":"11","author":"SV Rajkumar","year":"2010","unstructured":"Rajkumar SV, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11(1):29\u201337.","journal-title":"Lancet Oncol"},{"issue":"4","key":"1268_CR14","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1182\/blood-2007-11-124156","volume":"112","author":"S Sharma","year":"2008","unstructured":"Sharma S, Lichtenstein A. Dexamethasone-induced apoptotic mechanisms in myeloma cells investigated by analysis of mutant glucocorticoid receptors. Blood. 2008;112(4):1338\u201345.","journal-title":"Blood"},{"issue":"13","key":"1268_CR15","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.4161\/cc.25251","volume":"12","author":"MY Murray","year":"2013","unstructured":"Murray MY, et al. Attenuation of dexamethasone-induced cell death in multiple myeloma is mediated by miR-125b expression. Cell Cycle. 2013;12(13):2144\u201353.","journal-title":"Cell Cycle"},{"issue":"3","key":"1268_CR16","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1182\/blood.V75.3.715.715","volume":"75","author":"H Ishikawa","year":"1990","unstructured":"Ishikawa H, et al. Effect of glucocorticoids on the biologic activities of myeloma cells: inhibition of interleukin-1 beta osteoclast activating factor-induced bone resorption. Blood. 1990;75(3):715\u201320.","journal-title":"Blood"},{"key":"1268_CR17","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s13098-020-00583-7","volume":"12","author":"J Alessi","year":"2020","unstructured":"Alessi J, et al. Dexamethasone in the era of COVID-19: friend or foe? An essay on the effects of dexamethasone and the potential risks of its inadvertent use in patients with diabetes. Diabetol Metab Syndr. 2020;12:80.","journal-title":"Diabetol Metab Syndr"},{"issue":"1","key":"1268_CR18","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/0005-2736(91)90246-5","volume":"1066","author":"TM Allen","year":"1991","unstructured":"Allen TM, et al. Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim Biophys Acta. 1991;1066(1):29\u201336.","journal-title":"Biochim Biophys Acta"},{"issue":"19","key":"1268_CR19","first-page":"5135","volume":"52","author":"SK Huang","year":"1992","unstructured":"Huang SK, et al. Microscopic localization of sterically stabilized liposomes in colon carcinoma-bearing mice. Cancer Res. 1992;52(19):5135\u201343.","journal-title":"Cancer Res"},{"key":"1268_CR20","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/S0076-6879(05)91004-5","volume":"391","author":"SA Abraham","year":"2005","unstructured":"Abraham SA, et al. The liposomal formulation of doxorubicin. Methods Enzymol. 2005;391:71\u201397.","journal-title":"Methods Enzymol"},{"issue":"11","key":"1268_CR21","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1016\/j.ejca.2006.02.017","volume":"42","author":"C Jakob","year":"2006","unstructured":"Jakob C, et al. Angiogenesis in multiple myeloma. Eur J Cancer. 2006;42(11):1581\u201390.","journal-title":"Eur J Cancer"},{"issue":"2","key":"1268_CR22","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.imlet.2013.12.010","volume":"161","author":"D Ribatti","year":"2014","unstructured":"Ribatti D, et al. Macrophages in multiple myeloma. Immunol Lett. 2014;161(2):241\u20134.","journal-title":"Immunol Lett"},{"issue":"3","key":"1268_CR23","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.jconrel.2011.03.001","volume":"152","author":"W Hofkens","year":"2011","unstructured":"Hofkens W, et al. Intravenously delivered glucocorticoid liposomes inhibit osteoclast activity and bone erosion in murine antigen-induced arthritis. J Control Release. 2011;152(3):363\u20139.","journal-title":"J Control Release"},{"issue":"3","key":"1268_CR24","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2217\/17435889.1.3.297","volume":"1","author":"ML Immordino","year":"2006","unstructured":"Immordino ML, Dosio F, Cattel L. Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine. 2006;1(3):297\u2013315.","journal-title":"Int J Nanomedicine"},{"issue":"12","key":"1268_CR25","first-page":"1503","volume":"21","author":"YM Ning","year":"2007","unstructured":"Ning YM, et al. Liposomal doxorubicin in combination with bortezomib for relapsed or refractory multiple myeloma. Oncology (Williston Park). 2007;21(12):1503\u20138.","journal-title":"Oncology (Williston Park)"},{"issue":"3","key":"1268_CR26","doi-asserted-by":"publisher","first-page":"925","DOI":"10.2307\/2531693","volume":"45","author":"BE Storer","year":"1989","unstructured":"Storer BE. Design and analysis of phase I clinical trials. Biometrics. 1989;45(3):925\u201337.","journal-title":"Biometrics"},{"issue":"9","key":"1268_CR27","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1038\/sj.leu.2404284","volume":"20","author":"BG Durie","year":"2006","unstructured":"Durie BG, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467\u201373.","journal-title":"Leukemia"},{"key":"1268_CR28","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1002\/art.11140","volume":"48","author":"JM Metselaar","year":"2003","unstructured":"Metselaar JM, et al. Complete remission of experimental arthritis by joint targeting of glucocorticoids with long-circulating liposomes. Arthritis Rheum. 2003;48:2059\u201366.","journal-title":"Arthritis Rheum"},{"issue":"5","key":"1268_CR29","doi-asserted-by":"publisher","first-page":"419","DOI":"10.2165\/00003088-200342050-00002","volume":"42","author":"A Gabizon","year":"2003","unstructured":"Gabizon A, et al. Pharmacokinetics of pegylated liposomal doxorubicin: review of animal and human studies. Clin Pharmacokinet. 2003;42(5):419\u201336.","journal-title":"Clin Pharmacokinet"},{"issue":"6","key":"1268_CR30","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1007\/BF02455994","volume":"32","author":"ME Brady","year":"1987","unstructured":"Brady ME, et al. The pharmacokinetics of single high doses of dexamethasone in cancer patients. Eur J Clin Pharmacol. 1987;32(6):593\u20136.","journal-title":"Eur J Clin Pharmacol"},{"key":"1268_CR31","doi-asserted-by":"crossref","unstructured":"Spoorenberg SMC, et al. Pharmacokinetics of oral vs. intravenous dexamethasone in patients hospitalized with community-acquired pneumonia. Br J Clin Pharmacol. 2014;78(1):78\u201383.","DOI":"10.1111\/bcp.12295"},{"issue":"12","key":"1268_CR32","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1080\/17474086.2021.1983426","volume":"14","author":"P Tacchetti","year":"2021","unstructured":"Tacchetti P, et al. Emerging and current treatment combinations for transplant-ineligible multiple myeloma patients. Expert Rev Hematol. 2021;14(12):1085\u201398.","journal-title":"Expert Rev Hematol"},{"issue":"8","key":"1268_CR33","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1086\/605664","volume":"49","author":"M Nucci","year":"2009","unstructured":"Nucci M, et al. Infections in patients with multiple myeloma in the era of high-dose therapy and novel agents. Clin Infect Dis. 2009;49(8):1211\u201325.","journal-title":"Clin Infect Dis"},{"issue":"9461","key":"1268_CR34","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/S0140-6736(05)17989-6","volume":"365","author":"F Buttgereit","year":"2005","unstructured":"Buttgereit F, et al. Optimised glucocorticoid therapy: the sharpening of an old spear. Lancet. 2005;365(9461):801\u20133.","journal-title":"Lancet"},{"issue":"9","key":"1268_CR35","doi-asserted-by":"publisher","first-page":"1836","DOI":"10.3390\/ijms18091836","volume":"18","author":"F Luehder","year":"2017","unstructured":"Luehder F, et al. Novel drug delivery systems tailored for improved administration of glucocorticoids. Int J Mol Sci. 2017;18(9):1836.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"1268_CR36","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1080\/08982100801893978","volume":"18","author":"M Banciu","year":"2008","unstructured":"Banciu M, et al. Utility of targeted glucocorticoids in cancer therapy. J Liposome Res. 2008;18(1):47\u201357.","journal-title":"J Liposome Res"},{"issue":"2","key":"1268_CR37","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1593\/neo.04340","volume":"7","author":"RM Schiffelers","year":"2005","unstructured":"Schiffelers RM, et al. Liposome-encapsulated prednisolone phosphate inhibits growth of established tumors in mice. Neoplasia. 2005;7(2):118\u201327.","journal-title":"Neoplasia"},{"key":"1268_CR38","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/j.jconrel.2014.05.039","volume":"19","author":"B Ozbakir","year":"2014","unstructured":"Ozbakir B, et al. Liposomal corticosteroids for the treatment of inflammatory disorders and cancer. J Control Release. 2014;19:624\u201336.","journal-title":"J Control Release"},{"key":"1268_CR39","doi-asserted-by":"crossref","unstructured":"Metselaar JM, et al. Intravenous pegylated liposomal prednisolone outperforms intramuscular methylprednisolone in treating rheumatoid arthritis flares: a randomized controlled clinical trial. J Control Release. 2022;341:548\u201354.","DOI":"10.1016\/j.jconrel.2021.12.007"},{"issue":"7","key":"1268_CR40","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1111\/aos.14751","volume":"99","author":"SE Detiger","year":"2021","unstructured":"Detiger SE, et al. A pilot study on the use of prednisolone-encapsulated liposomes for the treatment of moderate-to-severe Graves\u2019 orbitopathy with reduced systemic steroid exposure. Acta Ophthalmol. 2021;99(7):797\u2013804.","journal-title":"Acta Ophthalmol"},{"issue":"8","key":"1268_CR41","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1016\/j.ekir.2020.05.030","volume":"5","author":"BM Voorzaat","year":"2020","unstructured":"Voorzaat BM, et al. A randomized trial of liposomal prednisolone (LIPMAT) to enhance radiocephalic fistula maturation: a pilot study. Kidney Int Rep. 2020;5(8):1327\u201332.","journal-title":"Kidney Int Rep"},{"issue":"5","key":"1268_CR42","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.845","volume":"9","author":"JPM Vrouwe","year":"2021","unstructured":"Vrouwe JPM, et al. An exploratory first-in-man study to investigate the pharmacokinetics and safety of liposomal dexamethasone at a 2- and 1-week interval in patients with metastatic castration resistant prostate cancer. Pharmacol Res Perspect. 2021;9(5):e00845.","journal-title":"Pharmacol Res Perspect"},{"issue":"6","key":"1268_CR43","doi-asserted-by":"publisher","first-page":"6396","DOI":"10.1021\/acsnano.8b07865","volume":"13","author":"JD Martin","year":"2019","unstructured":"Martin JD, et al. Dexamethasone increases cisplatin-loaded nanocarrier delivery and efficacy in metastatic breast cancer by normalizing the tumor microenvironment. ACS Nano. 2019;13(6):6396\u2013408.","journal-title":"ACS Nano"},{"issue":"8","key":"1268_CR44","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1002\/pros.22963","volume":"75","author":"J Kroon","year":"2015","unstructured":"Kroon J, et al. Liposomal delivery of dexamethasone attenuates prostate cancer bone metastatic tumor growth in vivo. Prostate. 2015;75(8):815\u201324.","journal-title":"Prostate"},{"issue":"3","key":"1268_CR45","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s12307-011-0072-9","volume":"4","author":"N Giuliani","year":"2011","unstructured":"Giuliani N, et al. Angiogenesis and multiple myeloma. Cancer Microenviron. 2011;4(3):325\u201337.","journal-title":"Cancer Microenviron"}],"container-title":["Drug Delivery and Translational Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-022-01268-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13346-022-01268-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-022-01268-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T20:10:12Z","timestamp":1677787812000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13346-022-01268-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,2]]},"references-count":45,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["1268"],"URL":"https:\/\/doi.org\/10.1007\/s13346-022-01268-6","relation":{},"ISSN":["2190-393X","2190-3948"],"issn-type":[{"value":"2190-393X","type":"print"},{"value":"2190-3948","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,2]]},"assertion":[{"value":"23 November 2022","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 January 2023","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Independent Ethics Committee at the Medical Faculty of RWTH Aachen University. Informed consent to participate was obtained from all individual participants included in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent to publish has been received from all study participants.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Josbert Metselaar declares a honorarium from Enceladus Pharmaceuticals; Amelie Boquoi has received speaker honoraria by BMS, AbbVie and Janssen, travel support by Takeda, and has served on advisory boards for GSK, Sanofi, Janssen, Takeda, Amgen, and BMS; Susanne Isfort has received consultant honoraria from Novartis, Pfizer, Incyte and travel support from Pfizer, Novartis, Hexal, Roche, Alexion, Mundipharma; Martina Crysandt has received speaker and consultant honoraria from Astra Zeneca, Novartis and travel support from Pfizer.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}