{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:22:38Z","timestamp":1789129358676,"version":"build-2803163510"},"reference-count":14,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2018,6,10]],"date-time":"2018-06-10T00:00:00Z","timestamp":1528588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2018,7,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The blood\u2013brain barrier (BBB) limits the access of drugs to the brain. Intensive research is being conducted on the development of nanoparticulate drug carriers that mediate transfer across the BBB. A question that has been neglected so far is the potential accumulation of the carrier in the brain upon long\u2010term exposure. Here, we address this question by implementing a kinetic model to relate drug loading, required concentration of drug in the brain, and drug clearance to the degradation half\u2010life of the carrier. As a test case with clinical relevance we chose poly\u2010lactic\u2010co\u2010glycolic\u2010acid (PLGA) as a carrier material and a chemotherapeutic for which the required parameters could be recovered from the literature. For methotrexate with a drug load of 8.5\u2009%, a required concentration of free drug of 1\u2005\u03bc<jats:sc>m<\/jats:sc>, a release from PLGA of 6\u2005hours, a drug clearance from the brain of 3\u2005hours and a half\u2010life of polymer degradation of 28\u2005days, a steady\u2010state accumulation of 1.3\u2005g polymer would be reached in the brain (1.5\u2005L) after seven months. While this number is surprisingly small, further physiological research is warranted to assess to which degree this will be in a tolerable range.<\/jats:p>","DOI":"10.1002\/cmdc.201800186","type":"journal-article","created":{"date-parts":[[2018,5,11]],"date-time":"2018-05-11T09:49:47Z","timestamp":1526032187000},"page":"1308-1310","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Modeling the Accumulation of Degradable Polymer Drug Carriers in the Brain"],"prefix":"10.1002","volume":"13","author":[{"given":"Celine","family":"Bolwerk","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Radboud Institute for Molecular Life Sciences Radboud University Medical Center  Geert Grooteplein 28 6525 GA Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa P. M. W. D.","family":"Govers","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Radboud Institute for Molecular Life Sciences Radboud University Medical Center  Geert Grooteplein 28 6525 GA Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Knol","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Radboud Institute for Molecular Life Sciences Radboud University Medical Center  Geert Grooteplein 28 6525 GA Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thom F.","family":"Oostendorp","sequence":"additional","affiliation":[{"name":"Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  6525 EN Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1395-6127","authenticated-orcid":false,"given":"Roland","family":"Brock","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Radboud Institute for Molecular Life Sciences Radboud University Medical Center  Geert Grooteplein 28 6525 GA Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,10]]},"reference":[{"key":"e_1_2_2_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1824"},{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-007-9379-0"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2011.10.028"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2016.07.003"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2017.08.155"},{"key":"e_1_2_2_6_1","first-page":"749","volume":"8","author":"Cai Q.","year":"2016","journal-title":"Am. 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