Background: The proteasome inhibitor bortezomib (BTZ), used in antineoplastic chemotherapy, must be diluted in NaCl 0.9% for injection and stored for no more than 3 hours in a syringe or 8 hours in a vial. Better information on its stability could improve storage.
Objective: To assess the stability of BTZ solution (1 mg/mL) in syringes and vials.
Methods: BTZ 1-mg/mL solutions were prepared by adding sterile NaCl 0.9% to Velcade vials containing 3.5 mg of lyophilized BTZ. Syringes were filled with 1 mL of solution and stored in the dark at 5 degrees C or 60 degrees C; others were not protected from light and stored at 22 degrees C. Velcade vials containing 1 mL of solution were stored at 5 degrees C in the dark. Samples were taken at various times over 23 days and assayed in duplicate. An HPLC method for assaying the stability of BTZ was validated. Appearance and pH were recorded.
Results: There was no color change or precipitation in the samples, and the pH was stable. Oxidation, light, and storage temperature all affected the chemical stability of BTZ. The mean concentrations of BTZ in syringes stored for 2, 3, and 5 days at 60, 22, and 5 degrees C were >95% of the initial concentration. The mean concentration of BTZ in vials stored for 5 days at 5 degrees C was >95% of the initial concentration.
Conclusions: BTZ stored refrigerated in vials or syringes and protected from light is chemically stable for 5 days after reconstitution.
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http://dx.doi.org/10.1345/aph.1E620 | DOI Listing |
Int J Biol Sci
January 2025
Department of Hematology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Chemoresistance is an important factor in multiple myeloma (MM) relapse and overall survival. However, the mechanism underlying resistance remains unclear. In this study, we identified adenine nucleotide translocase 3 (ANT3) as a novel biomarker and therapeutic target for MM progression and resistance to the proteasome inhibitor bortezomib (BTZ).
View Article and Find Full Text PDFJ Exp Clin Cancer Res
December 2024
Institute for Research On Cancer and Aging of Nice (IRCAN), CNRS UMR 7284, INSERM U1081, University Côte d'Azur, Nice, France.
Background: Multiple Myeloma (MM) is the second most common hematological malignancy, characterized by the accumulation of monoclonal plasmocytes in the bone marrow. Despite advancements with proteasome inhibitors, immunomodulatory agents, and CD38-targeting antibodies, MM remains largely incurable due to resistant clones and frequent relapses. The success of the proteasome inhibitor bortezomib (BTZ) in MM treatment highlights the critical role of the ubiquitin-proteasome system (UPS) in this disease.
View Article and Find Full Text PDFPLoS One
November 2024
Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
Mycobacterium tuberculosis is a lethal human pathogen, with the key flavoenzyme for catalyzing bacterial cell-wall biosynthesis, decaprenylphosphoryl-D-ribose oxidase (DprE1), considered an Achilles heal for tuberculosis (TB) progression. Inhibition of DprE1 blocks cell wall biosynthesis and is a highly promising antitubercular target. Macozinone (PBTZ169, a benzothiazinone (BTZ) derivative) is an irreversible DprE1 inhibitor that has attracted considerable attention because it exhibits an additive activity when combined with other anti-TB drugs.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. Electronic address:
Human serum albumin (HSA), a crucial plasma protein, plays a significant role in drug interactions within the bloodstream, bearing considerable clinical relevance. Bortezomib (BTZ) is a potent anti-cancer drug for multiple myeloma (MM) and mantle cell lymphoma (MC). The mechanism of BTZ transfer in the blood remains undetermined.
View Article and Find Full Text PDFMacromol Biosci
October 2024
Department of Polymer Science and Engineering, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China.
The therapeutic efficacy of bortezomib (BTZ) is often limited due to low solubility, poor stability in vivo and nonspecific toxicity. Herein, a kind of catechol-functionalized polyethylene glycol (mPEG-CA) is first synthesized and then mPEG-CA is readily used to conjugate with BTZ by the formation of dynamic boronate bonds to obtain PEGlyated BTZ prodrug (mPEG-CA-BTZ) with the ability of pH-controlled disassembly and drug release. The structure and morphology, physicochemical characteristics, drug loading, and release as well as in vitro cytotoxicity of mPEG-CA-BTZ nanoparticles are investigated in detail.
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