2017
DOI: 10.1371/journal.pone.0173247
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Polymer micelle formulation for the proteasome inhibitor drug carfilzomib: Anticancer efficacy and pharmacokinetic studies in mice

Abstract: Carfilzomib (CFZ) is a peptide epoxyketone proteasome inhibitor approved for the treatment of multiple myeloma (MM). Despite the remarkable efficacy of CFZ against MM, the clinical trials in patients with solid cancers yielded rather disappointing results with minimal clinical benefits. Rapid degradation of CFZ in vivo and its poor penetration to tumor sites are considered to be major factors limiting its efficacy against solid cancers. We previously reported that polymer micelles (PMs) composed of biodegradab… Show more

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Cited by 22 publications
(9 citation statements)
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“…The analytical conditions for Cfz were reported previously . Cfz–OH was quantified using the slightly modified analytical conditions via LC–MS/MS (1260 infinity HPLC system interfaced with 6430 Triple Quad LC–MS system, Agilent Technologies, Palo Alto, CA) in a positive ion mode.…”
Section: Methodsmentioning
confidence: 99%
See 1 more Smart Citation
“…The analytical conditions for Cfz were reported previously . Cfz–OH was quantified using the slightly modified analytical conditions via LC–MS/MS (1260 infinity HPLC system interfaced with 6430 Triple Quad LC–MS system, Agilent Technologies, Palo Alto, CA) in a positive ion mode.…”
Section: Methodsmentioning
confidence: 99%
“…The analytical conditions for Cfz were reported previously. 50 Cfz− OH was quantified using the slightly modified analytical conditions via LC−MS/MS (1260 infinity HPLC system interfaced with 6430 Triple Quad LC−MS system, Agilent Technologies, Palo Alto, CA) in a positive ion mode. The chromatic separation was performed using a Poroshell 120 EC-C18 column (4.6 × 50 mm 2 , 2.7 μm, Agilent Technologies, Palo Alto, CA) and an isocratic mobile phase composed of acetonitrile and water (75:25, v/v) at a flow rate of 0.3 mL/min.…”
Section: ■ Experimental Sectionmentioning
confidence: 99%
“…Nanomedicines provide a valuable means to tackle the solubility, stability, and systemic toxicity issues of chemical drugs. Interestingly, Doxil, Caelyx (liposomal doxorubicin), and Oncocort (liposomal dexamethasone phosphate) have already been used clinically or in clinical trials to treat MM . There are also attempts to develop nanosystems to improve delivery of proteasome inhibitors. For example, CFZ encapsulated in the poly­(ethylene glycol)–poly­(caprolactone) (PEG–PCL) diblock copolymer micelles revealed clearly better in vitro metabolic stability than CFZ-CD. , CFZ-loaded liposomes exhibited lower systemic toxicity and better tumor suppression than CFZ in MM xenograft mouse model . Very late antigen-4 (VLA-4) peptide-decorated liposomal CFZ demonstrated further enhancement in MM growth inhibition.…”
Section: Introductionmentioning
confidence: 99%
“…There was no much information available about degradation behaviour of Carfilzomib and identification of its degradants in literature, where only stability paper was available [7]. The characterization data was not described earlier but few LC-MS/MS methods about drug and its biological matrixes [8][9][10][11] available in the literature. The aim of present study was to investigate the stability studies of the API drug under stress conditions which was carried out according to the international conference on harmonization (ICH) guidelines [12][13][14][15][16], followed by separation of degradation products through Preparative HPLC, identification and characterisation by LCMS, HRMS & NMR.…”
Section: Introductionmentioning
confidence: 99%