دورية أكاديمية
Polymeric micelles loaded with carfilzomib increase tolerability in a humanized bone marrow-like scaffold mouse model.
| العنوان: | Polymeric micelles loaded with carfilzomib increase tolerability in a humanized bone marrow-like scaffold mouse model. |
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| المؤلفون: | Varela-Moreira A; Laboratory of Clinical Chemistry and Hematology (LKCH), University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands.; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands., van Straten D; Laboratory of Clinical Chemistry and Hematology (LKCH), University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands., van Leur HF; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands., Ruiter RWJ; Department of Hematology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1118, 1182, DB, Amsterdam, the Netherlands., Deshantri AK; Laboratory of Clinical Chemistry and Hematology (LKCH), University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands.; Biological Research Pharmacology Department, Sun Pharma Advanced Research Company Ltd., Vadodara, India., Hennink WE; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands., Fens MHAM; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands., Groen RWJ; Department of Hematology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1118, 1182, DB, Amsterdam, the Netherlands., Schiffelers RM; Laboratory of Clinical Chemistry and Hematology (LKCH), University Medical Center Utrecht, Heidelberglaan 100, 3584, CX, Utrecht, the Netherlands.; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, 3584, CG, Utrecht, the Netherlands. |
| المصدر: | International journal of pharmaceutics: X [Int J Pharm X] 2020 May 16; Vol. 2, pp. 100049. Date of Electronic Publication: 2020 May 16 (Print Publication: 2020). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101753452 Publication Model: eCollection Cited Medium: Internet ISSN: 2590-1567 (Electronic) Linking ISSN: 25901567 NLM ISO Abbreviation: Int J Pharm X Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier B.V., [2019]- |
| مستخلص: | Carfilzomib-loaded polymeric micelles (CFZ-PM) based on poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide) (mPEG-b-p(HPMA-Bz)) were prepared with the aim to improve the maximum tolerated dose of carfilzomib in a "humanized" bone marrow-like scaffold model. For this, CFZ-PM were prepared and characterized for their size, carfilzomib loading and cytotoxicity towards multiple myeloma cells. Further, circulation and tumor & tissue distribution of fluorescently labeled micelles were determined. Tolerability of CFZ-PM versus the clinical approved formulation - Kyprolis® - was assessed. CFZ-PM presented small diameter below 55 nm and low PDI < 0.1. Cy7-labeled micelles circulated for extended periods of time with over 80% of injected dose in circulation at 24 h after intravenous injection and 1.3% of the injected dose of Cy7-labeled micelles accumulated in myeloma tumor-bearing scaffolds. Importantly, CFZ-PM were well tolerated whereas Kyprolis® showed adverse effects. Kyprolis® dosed at the maximum tolerated dose, as well as CFZ-PM, did not show therapeutic benefit, while multiple myeloma cells showed sensitivity in vitro , underlining the importance of the bone marrow crosstalk in testing novel formulations. Overall, this work indicates that PM are potential drug carriers of carfilzomib. Competing Interests: The authors report no conflicts of interest. (© 2020 The Authors.) |
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| فهرسة مساهمة: | Keywords: Bone Marrow Microenvironment; Carfilzomib; Drug delivery; Multiple Myeloma; Polymeric micelles; Proteasome inhibitor |
| تواريخ الأحداث: | Date Created: 20200604 Latest Revision: 20200928 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7262453 |
| DOI: | 10.1016/j.ijpx.2020.100049 |
| PMID: | 32490374 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2590-1567 |
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| DOI: | 10.1016/j.ijpx.2020.100049 |