Nano-Encapsulation of Plitidepsin: In Vivo Pharmacokinetics, Biodistribution, and Efficacy in a Renal Xenograft Tumor Model
| dc.rights.license | open | |
| hal.structure.identifier | Laboratoire de Chimie des Polymères Organiques [LCPO] | |
| dc.contributor.author | DE OLIVEIRA, Hugo | |
| hal.structure.identifier | Laboratoire de Chimie des Polymères Organiques [LCPO] | |
| dc.contributor.author | THEVENOT, Julie | |
| hal.structure.identifier | Laboratoire de Chimie des Polymères Organiques [LCPO] | |
| hal.structure.identifier | Team 3 LCPO : Polymer Self-Assembly & Life Sciences | |
| dc.contributor.author | GARANGER, Elisabeth
IDREF: 089451740 | |
| hal.structure.identifier | Laboratoire de Chimie des Polymères Organiques [LCPO] | |
| dc.contributor.author | IBARBOURE, Emmanuel | |
| hal.structure.identifier | Pharma Mar SA, Sociedad Unipersonal, Madrid | |
| dc.contributor.author | CALVO, Pilar | |
| hal.structure.identifier | Pharma Mar SA, Sociedad Unipersonal, Madrid | |
| dc.contributor.author | AVILÉS, Pablo | |
| hal.structure.identifier | Pharma Mar SA, Sociedad Unipersonal, Madrid | |
| dc.contributor.author | JOSE GUILLEN, Maria | |
| hal.structure.identifier | Laboratoire de Chimie des Polymères Organiques [LCPO] | |
| hal.structure.identifier | Team 3 LCPO : Polymer Self-Assembly & Life Sciences | |
| dc.contributor.author | LECOMMANDOUX, Sebastien | |
| dc.date.accessioned | 2020 | |
| dc.date.available | 2020 | |
| dc.date.issued | 2014 | |
| dc.identifier.issn | 0724-8741 | |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/20185 | |
| dc.description.abstractEn | Plitidepsin is an antineoplasic currently in clinical evaluation in a phase III trial in multiple myeloma (ADMYRE). Presently, the hydrophobic drug plitidepsin is formulated using CremophorA (R), an adjuvant associated with unwanted hypersensitivity reactions. In search of alternatives, we developed and tested two nanoparticle-based formulations of plitidepsin, aiming to modify/improve drug biodistribution and efficacy. Using nanoprecipitation, plitidepsin was loaded in polymer nanoparticles made of amphiphilic block copolymers (i.e. PEG-b-PBLG or PTMC-b-PGA). The pharmacokinetics, biodistribution and therapeutic efficacy was assessed using a xenograft renal cancer mouse model (MRI-H-121 xenograft) upon administration of the different plitidepsin formulations at maximum tolerated multiple doses (0.20 and 0.25 mg/kg for CremophorA (R) and copolymer formulations, respectively). High plitidepsin loading efficiencies were obtained for both copolymer formulations. Considering pharmacokinetics, PEG-b-PBLG formulation showed lower plasma clearance, associated with higher AUC and Cmax than CremophorA (R) or PTMC-b-PGA formulations. Additionally, the PEG-b-PBLG formulation presented lower liver and kidney accumulation compared with the other two formulations, associated with an equivalent tumor distribution. Regarding the anticancer activity, all formulations elicited similar efficacy profiles, as compared to the CremophorA (R) formulation, successfully reducing tumor growth rate. Although the nanoparticle formulations present equivalent anticancer activity, compared to the CremophorA (R) formulation, they show improved biodistribution profiles, presenting novel tools for future plitidepsin-based therapies. | |
| dc.language.iso | en | |
| dc.publisher | American Association of Pharmaceutical Scientists | |
| dc.subject.en | BIWEEKLY PLITIDEPSIN | |
| dc.subject.en | MULTIPLE-MYELOMA | |
| dc.subject.en | SOLID TUMORS | |
| dc.subject.en | cancer therapy | |
| dc.subject.en | drug delivery | |
| dc.subject.en | nanomedicine | |
| dc.subject.en | plitidepsin | |
| dc.subject.en | polymersomes | |
| dc.subject.en | CELL LUNG-CANCER | |
| dc.subject.en | EVERY 2 WEEKS | |
| dc.subject.en | PHASE-II | |
| dc.subject.en | 2ND-LINE THERAPY | |
| dc.subject.en | INFUSION | |
| dc.subject.en | NANOPARTICLES | |
| dc.subject.en | ACTIVATION | |
| dc.title.en | Nano-Encapsulation of Plitidepsin: In Vivo Pharmacokinetics, Biodistribution, and Efficacy in a Renal Xenograft Tumor Model | |
| dc.type | Article de revue | |
| dc.identifier.doi | 10.1007/s11095-013-1220-3 | |
| dc.subject.hal | Chimie/Polymères | |
| bordeaux.journal | Pharmaceutical Research | |
| bordeaux.page | 983-991 | |
| bordeaux.volume | 31 | |
| bordeaux.hal.laboratories | Laboratoire de Chimie des Polymères Organiques (LCPO) - UMR 5629 | * |
| bordeaux.issue | 4 | |
| bordeaux.institution | Bordeaux INP | |
| bordeaux.institution | Université de Bordeaux | |
| bordeaux.peerReviewed | oui | |
| hal.identifier | hal-01373361 | |
| hal.version | 1 | |
| hal.origin.link | https://hal.archives-ouvertes.fr//hal-01373361v1 | |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Pharmaceutical%20Research&rft.date=2014&rft.volume=31&rft.issue=4&rft.spage=983-991&rft.epage=983-991&rft.eissn=0724-8741&rft.issn=0724-8741&rft.au=DE%20OLIVEIRA,%20Hugo&THEVENOT,%20Julie&GARANGER,%20Elisabeth&IBARBOURE,%20Emmanuel&CALVO,%20Pilar&rft.genre=article |
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