Folic acid grafted tofacitinib loaded targeted transfersomes for transdermal delivery against breast cancer

Abstract

The current study evaluates the efficacy of tofacitinib (Tofa) loaded folate grafted transfersomes (FA-CS-Tofa-Tfs) for transdermal delivery to treat breast cancer. Tofa-Tfs were prepared and optimized by using Box Behnken design of experiment and then coated with FA-CS by electrostatic interaction. FA-CS-Tofa-Tfs were subsequently embedded in Carbopol gel containing Eucalyptus oil (EO) as permeation enhancer to enhance drug bioavailability. The prepared formulation was then evaluated for physicochemical and in vitro characterization. FA-CS-Tofa-Tfs were spherical in shape with a vesicle size of 232.57 ± 5.95 nm, % entrapment efficiency (EE) of 86.89 ± 5.13, zeta potential of +22.17 ± 5.05 and release profile of the designed system presented sustained release of Tofa for 48 h. The ex vivo permeation studies displayed 10.30 folds enhanced permeation for FA-CS-Tofa-Tfs gel with EO when compared with Tofa gel. In vitro cytotoxicity study on MCF-7 breast cancer cells indicated 8.67 folds lower IC₅₀ value for FA-CS-Tofa-Tfs gel in contrast to Tofa. Flow cytometry results for cell apoptosis indicated significantly enhanced early and late apoptosis for FA-CS-Tofa-Tfs gel in comparison to pure Tofa. These substantial outcomes encourages that biocompatible FA-CS-Tofa-Tfs could be employed as a promising strategy to actively target and treat breast cancer via transdermal route.