α-Tocopheryl linolenate solid lipid nanoparticles for the encapsulation, protection, and release of the omega-3 polyunsaturated fatty acid: in vitro anti-melanoma activity evaluation

Abstract

The main target of this study was the preparation, characterization and antioxidant activity evaluation of α-tocopheryl linolenate based solid lipid nanoparticles (SLNs-TL), able to incorporate omega-3 α-linolenic acid, useful for the treatment of melanoma, a type of skin cancer. In particular, α-linolenic acid was successfully derivatized with α-tocopherol and the obtained compound was characterized by Fourier transform infrared (FT-IR) and by 1H NMR to confirm the ester linkage. Both the empty SLNs-TL that SLNs-TL-LIN, containing omega-3-linolenic acid, were prepared through the technique of the microemulsion. The nanoparticles were characterized for entrapment efficiency, size and shape. Their antioxidant activity was investigated in rat liver microsomal membranes in inhibiting the lipid peroxidation induced by tert-butyl hydroperoxide (tert-BOOH), which endogenously produces alkoxyl radicals by Fenton reactions. The obtained results indicate that the α-tocopherol, linked by ester bond to α-linolenic acid, maintains an excellent antioxidant activity. The encapsulation efficiency was equal to 77% and the polydispersity index 0.198 indicating a good dimensional distribution. Furthermore, the nanoparticles were tested in vitro for their cytotoxic activity against human melanoma cancer cell line C32. Both empty SLNs-TL and loaded SLNs-TL-LIN showed a high biological activity, being more effective than α-linolenic acid and α-tocopherol. The results indicated that these nanoparticles could provide the delivery and the protection of unstable molecules, such as α-linolenic acid, from degradation induced by mechanisms of oxidative stress.