%0 Journal Article
%T Some things old, new and borrowed: Delivery of dabrafenib and vemurafenib to melanoma cells via self-assembled nanomicelles based on an amphiphilic dendrimer.
%A Russi M
%A Valeri R
%A Marson D
%A Danielli C
%A Felluga F
%A Tintaru A
%A Skoko N
%A Aulic S
%A Laurini E
%A Pricl S
%J Eur J Pharm Sci
%V 180
%N 0
%D Jan 2023 1
%M 36273785
%F 5.112
%R 10.1016/j.ejps.2022.106311
%X 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 C18 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.