{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:48:18Z","timestamp":1792856898041,"version":"4.5.0"},"reference-count":29,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.ejps.2025.107246","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T06:52:46Z","timestamp":1756277566000},"page":"107246","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["TLD: An optimized liposomal doxorubicin formulation with small vesicle size for improved anti-tumor efficacy"],"prefix":"10.1016","volume":"213","author":[{"given":"Sime","family":"Brkic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Erni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younes","family":"Louaguenouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Carone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Henrik","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schreiber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8003-4432","authenticated-orcid":false,"given":"Andreas","family":"Zumbuehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Gabizon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9fan","family":"Halbherr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Peitsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejps.2025.107246_bib0002","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/0005-2736(91)90268-D","article-title":"Uptake of liposomes by cultured mouse bone marrow macrophages: influence of liposome composition and size","volume":"1061","author":"Allen","year":"1991","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.ejps.2025.107246_bib0003","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jconrel.2012.03.020","article-title":"Doxil(R)\u2013the first FDA-approved nano-drug: lessons learned","volume":"160","author":"Barenholz","year":"2012","journal-title":"J. Control Rel."},{"key":"10.1016\/j.ejps.2025.107246_bib0004","doi-asserted-by":"crossref","DOI":"10.1016\/j.addr.2025.115550","article-title":"Beyond the EPR effect: intravital microscopy analysis of nanoparticle drug delivery to tumors","volume":"219","author":"Belyaev","year":"2025","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejps.2025.107246_bib0005","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1023\/A:1008216430806","article-title":"The use of cardiac biopsy to demonstrate reduced cardiotoxicity in AIDS Kaposi\u2019s sarcoma patients treated with pegylated liposomal doxorubicin","volume":"9","author":"Berry","year":"1998","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.ejps.2025.107246_bib0006","doi-asserted-by":"crossref","first-page":"0016","DOI":"10.34133\/bmef.0016","article-title":"Principles of nanoparticle delivery to solid tumors","volume":"4","author":"Chan","year":"2023","journal-title":"BMe Front."},{"key":"10.1016\/j.ejps.2025.107246_bib0007","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nnano.2012.45","article-title":"Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner","volume":"7","author":"Chauhan","year":"2012","journal-title":"Nat. Nanotechnol."},{"key":"10.1016\/j.ejps.2025.107246_bib0008","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejca.2024.113588","article-title":"TLD-1, a novel liposomal doxorubicin, in patients with advanced solid tumors: dose escalation and expansion part of a multicenter open-label phase I trial (SAKK 65\/16)","volume":"201","author":"Colombo","year":"2024","journal-title":"Eur. J. Cancer"},{"key":"10.1016\/j.ejps.2025.107246_bib0009","doi-asserted-by":"crossref","first-page":"2677","DOI":"10.1007\/s11095-014-1364-9","article-title":"Biodistribution, tumor uptake and efficacy of 5-FU-loaded liposomes: why size matters","volume":"31","author":"Fanciullino","year":"2014","journal-title":"Pharm. Res."},{"key":"10.1016\/j.ejps.2025.107246_bib0010","first-page":"987","article-title":"Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes","volume":"54","author":"Gabizon","year":"1994","journal-title":"Cancer Res."},{"key":"10.1016\/j.ejps.2025.107246_bib0011","doi-asserted-by":"crossref","first-page":"419","DOI":"10.2165\/00003088-200342050-00002","article-title":"Pharmacokinetics of pegylated liposomal doxorubicin: review of animal and human studies","volume":"42","author":"Gabizon","year":"2003","journal-title":"Clin. Pharmacokinet."},{"key":"10.1016\/j.ejps.2025.107246_bib0012","article-title":"Thirty years from FDA approval of pegylated liposomal doxorubicin (Doxil\/Caelyx): an updated analysis and future perspective","volume":"4","author":"Gabizon","year":"2025","journal-title":"BMJ Oncol."},{"key":"10.1016\/j.ejps.2025.107246_bib0013","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2024.123942","article-title":"Understanding the In vitro-In Vivo Nexus: advanced correlation models predict clinical performance of liposomal doxorubicin","volume":"654","author":"Gan","year":"2024","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejps.2025.107246_bib0014","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0005-2736(93)90105-9","article-title":"Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases","volume":"1151","author":"Haran","year":"1993","journal-title":"Biochim. Biophys. Acta (BBA) - Biomembr."},{"key":"10.1016\/j.ejps.2025.107246_bib0015","doi-asserted-by":"crossref","first-page":"451","DOI":"10.7150\/ntno.75045","article-title":"Comparative effects of free doxorubicin, liposome encapsulated doxorubicin and liposome co-encapsulated alendronate and doxorubicin (PLAD) on the tumor immunologic milieu in a mouse fibrosarcoma model","volume":"6","author":"Islam","year":"2022","journal-title":"Nanotheranostics."},{"key":"10.1016\/j.ejps.2025.107246_bib0016","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nnano.2008.30","article-title":"Nanoparticle-mediated cellular response is size-dependent","volume":"3","author":"Jiang","year":"2008","journal-title":"Nat. Nanotechnol."},{"key":"10.1016\/j.ejps.2025.107246_bib0017","doi-asserted-by":"crossref","first-page":"14080","DOI":"10.1021\/acsnano.1c04510","article-title":"Specific endothelial cells govern nanoparticle entry into solid tumors","volume":"15","author":"Kingston","year":"2021","journal-title":"ACS. Nano."},{"key":"10.1016\/j.ejps.2025.107246_bib0018","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1002\/1097-0142(20000901)89:5<1037::AID-CNCR13>3.0.CO;2-Z","article-title":"Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma","volume":"89","author":"Lyass","year":"2000","journal-title":"Cancer"},{"key":"10.1016\/j.ejps.2025.107246_bib0019","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.addr.2012.10.002","article-title":"The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo","volume":"65","author":"Maeda","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejps.2025.107246_bib0020","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s00280-024-04679-z","article-title":"Population pharmacokinetics of TLD-1, a novel liposomal doxorubicin, in a phase I trial","volume":"94","author":"Mc Laughlin","year":"2024","journal-title":"Cancer Chemother. Pharmacol."},{"key":"10.1016\/j.ejps.2025.107246_bib0021","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics13010123","article-title":"Quantitative cryo-TEM reveals new structural details of doxil-like PEGylated liposomal doxorubicin formulation","volume":"13","author":"Nordstrom","year":"2021","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.ejps.2025.107246_bib0022","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/j.1552-4604.1996.tb04152.x","article-title":"Doxorubicin encapsulated in liposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi's sarcoma","volume":"36","author":"Northfelt","year":"1996","journal-title":"J. Clin. Pharmacol."},{"key":"10.1016\/j.ejps.2025.107246_bib0023","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1093\/annonc\/mdh097","article-title":"Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX\/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer","volume":"15","author":"O'Brien","year":"2004","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.ejps.2025.107246_bib0024","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1038\/s41563-020-0755-z","article-title":"The dose threshold for nanoparticle tumour delivery","volume":"19","author":"Ouyang","year":"2020","journal-title":"Nat. Mater."},{"key":"10.1016\/j.ejps.2025.107246_bib0025","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1023\/A:1008365716693","article-title":"Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg\/m2","volume":"11","author":"Safra","year":"2000","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.ejps.2025.107246_bib0026","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/s41563-019-0566-2","article-title":"The entry of nanoparticles into solid tumours","volume":"19","author":"Sindhwani","year":"2020","journal-title":"Nat. Mater."},{"key":"10.1016\/j.ejps.2025.107246_bib0027","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1007\/s00216-017-0527-z","article-title":"Zeta potential: a case study of cationic, anionic, and neutral liposomes","volume":"409","author":"Smith","year":"2017","journal-title":"Anal. Bioanal. Chem."},{"key":"10.1016\/j.ejps.2025.107246_bib0028","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1021\/acsomega.7b01235","article-title":"Cardinal role of intraliposome doxorubicin-sulfate nanorod crystal in doxil properties and performance","volume":"3","author":"Wei","year":"2018","journal-title":"ACS. Omega"},{"key":"10.1016\/j.ejps.2025.107246_bib0029","doi-asserted-by":"crossref","first-page":"e1519","DOI":"10.1002\/wnan.1519","article-title":"Strategies to improve tumor penetration of nanomedicines through nanoparticle design","volume":"11","author":"Zhang","year":"2019","journal-title":"Wiley. Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"10.1016\/j.ejps.2025.107246_bib0030","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41565-023-01323-4","article-title":"Machine-learning-assisted single-vessel analysis of nanoparticle permeability in tumour vasculatures","volume":"18","author":"Zhu","year":"2023","journal-title":"Nat. Nanotechnol."}],"container-title":["European Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098725002441?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0928098725002441?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T13:26:56Z","timestamp":1757770016000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0928098725002441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":29,"alternative-id":["S0928098725002441"],"URL":"https:\/\/doi.org\/10.1016\/j.ejps.2025.107246","relation":{},"ISSN":["0928-0987"],"issn-type":[{"value":"0928-0987","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"TLD: An optimized liposomal doxorubicin formulation with small vesicle size for improved anti-tumor efficacy","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejps.2025.107246","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"107246"}}