Liposomes loaded with histone deacetylase inhibitors for breast cancer therapy

Autor: Sylviane Lesieur, Giorgia Urbinati, Véronique Marsaud, Jack-Michel Renoir, Elias Fattal, Vincent Plassat
Přispěvatelé: Physico-chimie, pharmacotechnie, biopharmacie (PCPB), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2010
Předmět:
Chemical Phenomena
medicine.drug_class
Pharmaceutical Science
Antineoplastic Agents
Breast Neoplasms
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Pharmacology
Biology
Hydroxamic Acids
03 medical and health sciences
Drug Delivery Systems
0302 clinical medicine
Drug Stability
In vivo
Cell Line
Tumor
medicine
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Particle Size
Cytotoxicity
030304 developmental biology
Drug Carriers
Sulfonamides
0303 health sciences
Liposome
Estradiol
Histone deacetylase inhibitor
Estrogen Receptor alpha
3. Good health
Histone Deacetylase Inhibitors
[SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology
Trichostatin A
Biochemistry
SKBR3
030220 oncology & carcinogenesis
Liposomes
Female
Histone deacetylase
Drug carrier
medicine.drug
Zdroj: International Journal of Pharmaceutics
International Journal of Pharmaceutics, Elsevier, 2010, 397 (1-2), pp.184-193. ⟨10.1016/j.ijpharm.2010.06.046⟩
ISSN: 0378-5173
Popis: International audience; Histone deacetylase (HDAC) inhibitors (HDACi) of the class I trichostatin A (TSA), CG1521 (CG), and PXD101 (PXD) were incorporated at a high rate (approximately 1mM) in liposomes made of egg phosphatidylcholine/cholesterol/distearoylphosphoethanolamine-polyethylenglycol(2000) (64:30:6). Physicochemical parameters (size, zeta potential, loading, stability, release kinetics) of these HDACi-loaded pegylated liposomes were optimized and their cytotoxicity (MTT test) was measured in MCF-7, T47-D, MDA-MB-231 and SkBr3 breast cancer cell lines. In MCF-7 cells, TSA and PXD were efficient inducers of proteasome-mediated estradiol receptor alpha degradation and they both affected estradiol-induced transcription (TSA>PXD) contrary to CG. Moreover, TSA most efficiently altered breast cancer cell viability as compared to the free drug, CG-liposomes being the weakest, while unloaded liposomes had nearly no cytotoxicity. Pegylated liposomes loaded with TSA or PXD remained stable in size, charge and biological activity for one month when stored at 4 degrees C. All HDACi-loaded liposomes released slowly the encapsulated drug in vitro, CG-loaded liposomes showed the slowest release kinetic. These formulations could improve the efficacy of HDACi not only in breast cancers but also in other solid tumors because most of these drugs are poor water soluble and unstable in vivo, and their administration remains a challenge.
Databáze: OpenAIRE
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