Therapeutic Potential of New 4-hydroxy-tamoxifen-Loaded pH-gradient Liposomes in a Multiple Myeloma Experimental Model

Autor: Véronique Marsaud, Elias Fattal, Silvia Arpicco, Davide Audisio, Vincent Plassat, Giorgia Urbinati, Jack-Michel Renoir, Brigitte Sola
Přispěvatelé: Physico-chimie, pharmacotechnie, biopharmacie (PCPB), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), DSTF - University of Turin, University of Turin, Biologie moléculaire et cellulaire de la signalisation (BMCS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)
Rok vydání: 2009
Předmět:
pH-gradient Stealth liposomes
medicine.medical_specialty
Biodistribution
[SDV]Life Sciences [q-bio]
Mice
Nude
Pharmaceutical Science
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Pharmacology
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
In vivo
Cell Line
Tumor
Internal medicine
medicine
Animals
Humans
Pharmacology (medical)
ComputingMilieux_MISCELLANEOUS
Active metabolite
030304 developmental biology
0303 health sciences
Liposome
business.industry
Cell growth
Organic Chemistry
Proton-Motive Force
Xenograft Model Antitumor Assays
3. Good health
Disease Models
Animal
Tamoxifen
[SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology
Endocrinology
chemistry
030220 oncology & carcinogenesis
Dipalmitoylphosphatidylcholine
Liposomes
Toxicity
Molecular Medicine
Female
Nanocarriers
Multiple Myeloma
business
Biotechnology
Zdroj: Pharmaceutical Research
Pharmaceutical Research, American Association of Pharmaceutical Scientists, 2010, ⟨10.1007/s11095-009-0023-z⟩
ISSN: 1573-904X
0724-8741
Popis: To determine the better liposomal formulation incorporating the active metabolite of tamoxifen, 4-hydroxy-tamoxifen (4HT) and the biological impact of 4HT-pH-gradient liposomes on response to in vivo treatment. Several pegylated liposomes were formulated by varying the composition of lipids, increasing external pH from 7.4 to 9.0 and doubling the lipid concentration. Dipalmitoylphosphatidylcholine / cholesterol / distearoylphosphoethanolamine poly(ethylene)glycol liposomes (DL-9 liposomes) were chosen for their physico-chemical properties. Toxicity and release kinetics were assessed in breast cancer MCF-7 as well as in multiple myeloma (MM) cells. In vivo antitumor activity and bio-distribution were measured in the RPMI8226 MM model. Compared to conventional non-pH-gradient liposomes, 4HT-DL-9 liposomes resulted in concentration of up to 1 mM 4HT, greater stability, relative toxicity and slow 4HT release. Intravenous injections of 4HT-DL-9 liposomes at 4 mg/kg/week blocked MM tumor growth. Ki67 and CD34 labeling decreased in treated tumors, concomitantly with increase of activated caspase-3 supporting a cell proliferation arrest, a decrease of tumor vasculature and the induction of tumor cell death. This antitumor effect was assumed to be the result of a modified biodistribution of 4HT once trapped in DL-9 liposomes. Such 4HT-containing pH-gradient Stealth® nanocarriers could be helpful for MM treatment.
Databáze: OpenAIRE
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