دورية أكاديمية
Liposomal dexamethasone inhibits tumor growth in an advanced human-mouse hybrid model of multiple myeloma.
| العنوان: | Liposomal dexamethasone inhibits tumor growth in an advanced human-mouse hybrid model of multiple myeloma. |
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| المؤلفون: | Deshantri AK; Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands; Biological Research Pharmacology Department, Sun Pharma Advanced Research Company Ltd., Vadodara, India., Fens MH; Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands., Ruiter RWJ; Department of Hematology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands., Metselaar JM; Enceladus Pharmaceuticals, Naarden, The Netherlands; Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany., Storm G; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Department of Biomaterials Science and Technology, University of Twente, Enschede, The Netherlands., van Bloois L; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands., Varela-Moreira A; Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands., Mandhane SN; Biological Research Pharmacology Department, Sun Pharma Advanced Research Company Ltd., Vadodara, India., Mutis T; Department of Hematology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands., Martens ACM; Department of Hematology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands., Groen RWJ; Department of Hematology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands., Schiffelers RM; Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. Electronic address: R.M.Schiffelers@uu.nl. |
| المصدر: | Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2019 Feb 28; Vol. 296, pp. 232-240. Date of Electronic Publication: 2019 Jan 22. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier Science Publishers, 1984- |
| مواضيع طبية MeSH: | Antineoplastic Agents, Hormonal/*administration & dosage , Dexamethasone/*administration & dosage , Glucocorticoids/*administration & dosage , Multiple Myeloma/*drug therapy, Animals ; Body Weight/drug effects ; Bone and Bones/metabolism ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Humans ; Liposomes ; Mice, Knockout ; Multiple Myeloma/metabolism ; Multiple Myeloma/pathology ; Tissue Distribution ; Tumor Burden/drug effects |
| مستخلص: | Glucocorticoids are the cornerstone in the clinic for treatment of hematological malignancies, including multiple myeloma. Nevertheless, poor pharmacokinetic properties of glucocorticoids require high and frequent dosing with the off-target adverse effects defining the maximum dose. Recently, nanomedicine formulations of glucocorticoids have been developed that improve the pharmacokinetic profile, limit adverse effects and improve solid tumor accumulation. Multiple myeloma is a hematological malignancy characterized by uncontrolled growth of plasma cells. These tumors initiate increased angiogenesis and microvessel density in the bone marrow, which might be exploited using nanomedicines, such as liposomes. Nano-sized particles can accumulate as a result of the increased vascular leakiness at the bone marrow tumor lesions. Pre-clinical screening of novel anti-myeloma therapeutics in vivo requires a suitable animal model that represents key features of the disease. In this study, we show that fluorescently labeled long circulating liposomes were found in plasma up to 24 h after injection in an advanced human-mouse hybrid model of multiple myeloma. Besides the organs involved in clearance, liposomes were also found to accumulate in tumor bearing human-bone scaffolds. The therapeutic efficacy of liposomal dexamethasone phosphate was evaluated in this model showing strong tumor growth inhibition while free drug being ineffective at an equivalent dose (4 mg/kg) regimen. The liposomal formulation slightly reduced total body weight of myeloma-bearing mice during the course of treatment, which appeared reversible when treatment was stopped. Liposomal dexamethasone could be further developed as monotherapy or could fit in with existing therapy regimens to improve therapeutic outcomes for multiple myeloma. (Copyright © 2019. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: Bone marrow; Dexamethasone; Drug delivery; EPR effect; Liposomes; Multiple myeloma; Tumor microenvironment |
| المشرفين على المادة: | 0 (Antineoplastic Agents, Hormonal) 0 (Glucocorticoids) 0 (Liposomes) 7S5I7G3JQL (Dexamethasone) |
| تواريخ الأحداث: | Date Created: 20190126 Date Completed: 20200522 Latest Revision: 20200522 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.jconrel.2019.01.028 |
| PMID: | 30682443 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-4995 |
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| DOI: | 10.1016/j.jconrel.2019.01.028 |