Phosphatidyldiglycerol-Based Thermosensitive Liposomes Show Superior Therapeutic Efficacy Against Muscle-Invasive Bladder Cancer In Vivo

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (PD37)1 Sep 2021PD37-08 PHOSPHATIDYLDIGLYCEROL-BASED THERMOSENSITIVE LIPOSOMES SHOW SUPERIOR THERAPEUTIC EFFICACY AGAINST MUSCLE-INVASIVE BLADDER CANCER IN VIVO Iris Brummelhuis, Michiel Simons, Lars Lindner, Simone Kort, Sytse de Jong, Martin Hossann, Alfred Witjes, and Egbert Oosterwijk Iris BrummelhuisIris Brummelhuis More articles by this author , Michiel SimonsMichiel Simons More articles by this author , Lars LindnerLars Lindner More articles by this author , Simone KortSimone Kort More articles by this author , Sytse de JongSytse de Jong More articles by this author , Martin HossannMartin Hossann More articles by this author , Alfred WitjesAlfred Witjes More articles by this author , and Egbert OosterwijkEgbert Oosterwijk More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002047.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recommended treatments for muscle-invasive bladder cancer (MIBC) are associated with substantial morbidity. Hyperthermia (HT) triggered drug release from phosphatidyldiglycerol-based thermosensitive liposomes (DPPG2-TSL) might prevent surgical bladder removal and toxicity from systemic chemotherapy. We aimed to assess the efficacy of DPPG2-TSL encapsulated doxorubicin (DOX; DPPG2-TSL-DOX) combined with bladder HT, compared to free systemic and intravesical DOX, in a syngeneic orthotopic rat urothelial carcinoma model. METHODS: A total of 191 female Fischer F344 rats were used. Bladder tumors were initiated by inoculation of AY-27 cells and tumor bearing rats were selected with cystoscopy and semi-randomized over treatment groups. At day 5 and 8, animals were treated with 2 mg/kg DOX in different treatment modalities: intravenous (iv) DPPG2-TSL-DOX with HT, iv free DOX without HT, intravesical DOX without HT, intravesical DOX with HT or no treatment (control group), respectively. Animals were euthanized at day 14 and complete tumor response was assessed by histopathological evaluation. RESULTS: Treatment with iv DPPG2-TSL-DOX with HT resulted in the highest rate of animals with complete tumor response of 70%, which was significantly better than iv free DOX (18%, p=0.02) and no treatment (0%, p=0.001), and non-significantly better than intravesical DOX with (43%, p=0.35) or without HT (50%, p=0.41; Figure 1). All rats receiving intravesical DOX with HT (7/7) and 24% (5/21) of rats treated with DPPG2-TSL-DOX containing the same DOX dose with HT had to be euthanized before day 14 because of >15% body weight loss, while some rats showed dilated ureters (3/7 and 4/21) and urine retention (2/7 and 1/21, respectively).Figure 1. Tumor stage as determined by histopathological evaluation per group. Green colored parts of bars represent T1 tumors, and purple T2. CONCLUSIONS: Treatment with DPPG2-TSL-DOX combined with intravesical HT outperformed systemic and intravesical DOX in a syngeneic orthotopic rat UC model. There might be a role for DPPG2-TSL encapsulating chemotherapeutics in treatment of MIBC in the future. Source of Funding: This study was partially sponsored by Thermosome © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e658-e658 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Iris Brummelhuis More articles by this author Michiel Simons More articles by this author Lars Lindner More articles by this author Simone Kort More articles by this author Sytse de Jong More articles by this author Martin Hossann More articles by this author Alfred Witjes More articles by this author Egbert Oosterwijk More articles by this author Expand All Advertisement Loading ...