8-Hydroxyquinoline platinum(II)-loaded nanostructured lipid carriers targeted with riboflavin: synthesis and evaluation of the antitumoral activity

BOZTEPE, T.; ISLAN, G.A.; GAMBARO R.; CASTRO GR; LEON I.E

Jornada; Fronteras en nanobiotecnologia III; 2022

Platinum-based drugs are the anticancer agents that have been used to treat numerous kinds of cancer including colorectal, testicular, lung, ovarian, cervical, and head and neck [1]. Even though these drugs are used effectively in clinical applications, they may cause dose-limiting toxicity, chemoresistance. Drug delivery systems are designed to overcome the drawbacks of anticancer agents by increasing their cytotoxic effect by accumulating in the tumor area without creating damage in healthy tissues. Nanostructured lipid carriers (NLC) allow enhanced drug loading capacity and stability [2]. It has been reported that riboflavin transporters demonstrated up-regulation in several tumor types including colon carcinoma cells [3]. Riboflavin (RFV) could be a potential targeting molecule for active drug delivery. The drug 8-hydroxyquinoline platinum(II) (8HQ-Pt) loaded NLCs targeted with RFV were synthesized by the ultrasonication technique. Three NLC formulations were designed with different ratios of RFV added to the lipidic or the aqueous phases. While RFV (10 mg) was added to the first formulation (R1-8HQ-Pt-NLC) into aqueous phase, in the second formulation (R2-8HQ-Pt-NLC) the RVF (10 mg) was incorporated directly into the lipid phase, whereas in the third one (R3-8HQ-Pt-NLC) 5 mg of RVF was incorporated in the aqueous phase and 5 mg of RFV in the lipid phase before mixing. Cytotoxicity, cell uptake, and apoptosis assays against the human colon adenocarcinoma cell line HT-29 were investigated. When the antitumor activity of the formulations was compared with the free 8HQ-Pt drug, all the RFV-targeted 8HQ-Pt-loaded formulations showed a higher cytotoxic effect (except at 2.5 µM) (Figure 1). R1-8HQ-Pt-NLC exhibited the highest cellular uptake (89.5%) in comparison to R2-8HQ-Pt-NLC (25.5%) and R3-8HQ-Pt-NLC (47.7%). Also, R1-8HQ-Pt-NLC showed higher levels of apoptosis than the free 8HQ-Pt. As a conclusion, we presented that RFV targeting enhanced the antitumoral activity of NLC.