In Vitro transdermal delivery of sesamol using oleic acid chemically-modified gelatin nanoparticles as a potential breast cancer medication

Abstract

In this study, gelatin was conjugated to oleic acid, a known skin penetration enhancer, by means of an amidation reaction. The reaction was performed in the presence of carbodiimide/N-hydroxysuccinimide as activators in order to form a gelatin oleic acid conjugate. The successful synthesis of this conjugate was confirmed by FTIR and 1H NMR. Moreover, oleic-acid conjugated nanoparticles were prepared by the single desolvation reaction. Sesamol, a natural anticancer drug, was loaded into the nanoparticles in-process. A small particle size of 185 nm ± 2.6, low PDI (0.0365 ± 0.0165) and relatively high entrapment efficiency (44.6% ± 3.8) associated with a drug loading approaching 2.23 mg ± 0.19 were achieved. The in vitro release of sesamol from the newly developed system compared to the sesamol solution was assessed. In vitro Permeation of sesamol was performed through albino mice skin using a newly developed UPLC-MS/MS method where the oleic acid-conjugated gelatin nanoparticles demonstrated the best permeation results. Cytotoxicity studies on MCF-7 breast cancer cells were performed where the newly developed nanoparticles scored the lowest IC50 of 595 μM ± 32.3. As a conclusion, the newly developed system was successful in the transdermal delivery of sesamol and the cytotoxicity of the new formulations was confirmed.