Antitumoral Activity of Novel 8-Oxyquinolinate-Platinum(II)-Loaded Nanostruc-tured Lipid Carriers Targeted with Riboflavin.

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

La Plata

Congreso; V Jornadas de Química Inorgánica Prof. Aymonino; 2022

Platinum anticancer drugs have been utilized for decades to cure various types of cancer including testicular, cervical, ovarian, colorectal, bladder, lung, head, and neck cancer. However, dose-limiting toxicity, chemoresistance, drug degradation, low solubility consequently low bioavailability appears as some of the limitations to the use of platinum drugs in clinical applications. Drug delivery systems are developed to overcome the disadvantages of anticancer drugs by improving their antiproliferative effect by accumulating in the tumor area without damaging the healthy tissues [1]. Nanostructured lipid carriers (NLC) are one of the most promising systems for drug delivery as they have a high capacity to load drugs and also increase their apparent solubility, especially if they are hydrophobic molecules [2]. Riboflavin is a water-soluble molecule and it has been reported that its transporters exhibited up-regulation in several tumor types including colon carcinoma cells [3]. This work aims to enhance the availability of 8-QO-Pt in physiological environments through efficient encapsulation to achieve an improved antitumoral activity of RFV-functionalized 8-QO-Pt-loaded NLC. 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 (R1-8-QO-Pt-NLC) into the aqueous phase, in the second formulation (R2-8-QO-Pt-NLC) the RVF (10 mg) was incorporated directly into the lipid phase, whereas in the third one (R3-8-QO-Pt-NLC) 5 mg of RVF was incorporated in the aqueous phase and 5 mg of RFV in the lipid phase before mixing. All the RFV-functionalized 8-QO-Pt-loaded formulations displayed a higher cytotoxic effect in comparison to the free 8-QO-Pt. R1-8-QO-Pt-NLC exhibited the highest cellular uptake (89.5%) in comparison to R2-8-QO-Pt-NLC (25.5%) and R3-8-QO-Pt-NLC (47.7%). Also, R1-8-QO-Pt-NLC showed a higher level of apoptosis than the free 8-QO-Pt. The hemotoxicity assay proved that all the formulations are in an acceptable and low range of hemotoxicity.