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In vitro evaluation of NA1-115-7-loaded nanoemulsions, an MCL-1-specific inhibitor of natural origin, intended to treat B-cell lymphoproliferative disorders after oral administration
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DOI：10.1016/j.ijpharm.2022.122433.png)
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Abstract
En 中文
MCL-1, an anti-apoptotic member of the BCL-2 protein family, is overexpressed in many types of cancer and contributes to chemotherapy resistance. The drimane derivative NA1-115-7 is a natural compound isolated from Zygogynum pancheri that can be considered as a very promising lead for treating MCL-1-dependent he-matological malignancies. As this drug suffers from low stability in acidic conditions and poor aqueous solubility, we evaluated the potential oral use of NA1-115-7 by encapsulating it in lipid nanoemulsions (NA-NEs) prepared by spontaneous emulsification. NA-NEs showed a particle size of 41.9 +/- 2.2 nm, PDI of 0.131 +/- 0.016, zeta potential of -5.8 +/- 3.4 mV, encapsulation efficiency of approximately 100 % at a concentration of 24 mM. The stability of NA-1-115-7 was sixfold higher than that of the unencapsulated drug in simulated gastric fluid. NA-NEs significantly restored apoptosis and halved the effective doses of NA1-115-7 on BL2, a Burkitt lymphoma cell line, without toxicity in normal cells. Such a drug-delivery system appears to be particularly interesting for the oral administration of NA1-115-7, as it improves its solubility and stability, as well as efficacy, by reducing the therapeutic dose, making it possible to further consider in-vivo studies of this promising drug in BL2 xenografted mice.
Keywords:
BIOAVAILABILITY
PERMEABILITY
SOLUBILITY
MCL-1
STRATEGIES
DESIGN
PAMPA
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