A targeted drug delivery system of anti-cancer agents based on folic acid-cyclodextrin-long polymer functionalized silica nanoparticles

Targeted drug delivery systems (TDDSs) have been exploited to improve the efficacy of anticancer agents by increasing their concentration in tumor cells relative to normal cells. This leads to administration of required amount of drug with low toxicities which usually occur with conventional chemotherapeutic agents. Herein, a TDDS based on silica nanoparticles (NPs) was prepared for cancer cell targeting. The NPs were loaded with a combination therapy of thymoquinone and melatonin (TQ-MLT) then conjugated with a long polymer and carboxymethyl-β-cyclodextrin (CM-β-CD). The folic acid (FA) was then embedded into CD cavity via host guest interaction. The NPs were characterized using fourier transform infrared spectroscopy (FT-IR) and dynamic light scattering (DLS). Drug encapsulation efficiency (EE) and loading capacity (LC) were measured using UVspectrophotometer and thermal gravimetric analysis (TGA). The EE of the NPs before the surface modification (84%) was higher than after modification (75%). The results of in vitro drug release showed that the release rate of (TQ-MLT) from conjugated NPs was slower than the free drug. The in vitro cell viability assay confirmed that drug loaded-FA conjugated NPs were more toxic to HeLa cells compared to unconjugated NPs and the free drug.

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