PEGylated solid lipid nanoparticles for brain delivery of lipophilic kiteplatin Pt(IV) prodrugs: An in vitro study

Here, polyethylene glycol (PEG)-stabilized solid lipid nanoparticles (SLNs) containing Pt(IV) prodrugs derived from kiteplatin were designed and proposed as novel nanoformulations potentially useful for the treatment of glioblastoma multiforme. Four different Pt(IV) prodrugs were synthesized, starting from kiteplatin by the addition of two carboxylate ligands with different length of the alkyl chains and lipophilicity degree, and embedded in the core of PEG-stabilized SLNs composed of cetyl palmitate. The SLNs were extensively characterized by complementary optical and morphological techniques. The results proved the formation of SLNs characterized by average size under 100 nm and dependence of drug encapsulation efficiency on the lipophilicity degree of the tested Pt(IV) prodrugs. A monolayer of immortalized human cerebral microvascular endothelial cells (hCMEC/D3) was used as in vitro model of blood-brain barrier (BBB) to evaluate the ability of the SLNs to penetrate the BBB. For this purpose, optical traceable SLNs were achieved by co-incorporation of Pt(IV) prodrugs and luminescent carbon dots (C-Dots) in the SLNs. Finally, an in vitro study was performed by using a human glioblastoma cell line (U87), to investigate on the antitumor efficiency of the SLNs and on their improved ability to be cell internalized respect to the free Pt(IV) prodrugs.