Some things old, new and borrowed: Delivery of dabrafenib and vemurafenib to melanoma cells via self-assembled nanomicelles based on an amphiphilic dendrimer.

Autor: Russi M; Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS) - DEA, University of Trieste, Piazzale Europa 1, Trieste 34127, Italy., Valeri R; Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS) - DEA, University of Trieste, Piazzale Europa 1, Trieste 34127, Italy., Marson D; Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS) - DEA, University of Trieste, Piazzale Europa 1, Trieste 34127, Italy., Danielli C; Department of Chemical and Pharmaceutical Sciences, DSCF, University of Trieste, Via Giorgeri 1, Trieste 34127, Italy., Felluga F; Department of Chemical and Pharmaceutical Sciences, DSCF, University of Trieste, Via Giorgeri 1, Trieste 34127, Italy., Tintaru A; Aix Marseille Univ, CNRS - Centre Interdisciplinaire de Nanosciences de Marseille (CINaM) UMR 7325 - Département IMMF - Campus Luminy, 163, Avenue de Luminy, Marseille 13288, France., Skoko N; Biotechnology Development Unit, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy., Aulic S; Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS) - DEA, University of Trieste, Piazzale Europa 1, Trieste 34127, Italy; Biotechnology Development Unit, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy., Laurini E; Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS) - DEA, University of Trieste, Piazzale Europa 1, Trieste 34127, Italy. Electronic address: erik.laurini@dia.units.it., Pricl S; Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS) - DEA, University of Trieste, Piazzale Europa 1, Trieste 34127, Italy; Department of General Biophysics, University of Łódź, ul. Pomorska 141/143, Łódź 90-236, Poland.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2023 Jan 01; Vol. 180, pp. 106311. Date of Electronic Publication: 2022 Oct 20.
DOI: 10.1016/j.ejps.2022.106311
Abstrakt: Two clinically approved anticancer drugs targeting BRAF in melanoma patients - dabrafenib (DAB) and vemurafenib (VEM) - have been successfully encapsulated into nanomicelles formed upon self-assembly of an amphiphilic dendrimer AD based on two C 18 aliphatic chains and a G2 PAMAM head. The process resulted in the formation of well-defined (∼10 nm) core-shell nanomicelles (NMs) with excellent encapsulation efficiency (∼70% for DAB and ∼60% for VEM) and good drug loading capacity (∼27% and ∼24% for DAB and VEM, respectively). Dynamic light scattering (DLS), transmission electron microscopy (TEM), small-angle x-ray scattering (SAXS), nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC), and molecular simulation (MS) experiments were used, respectively, to determine the size and structure of the empty and drug-loaded nanomicelles (DLNMs), along with the interactions between the NMs and their cargoes. The in vitro release data revealed profiles governed by Fickian diffusion; moreover, for both anticancer molecules, an acidic environment (pH = 5.0) facilitated drug release with respect to physiological pH conditions (pH = 7.4). Finally, both DAB- and VEM-loaded NMs elicited enhanced response with respect to free drug treatments in 4 different melanoma cell lines.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
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