Design of topical nanostructured lipid carrier of silymarin and its effect on 7,12-dimethylbenz[a]anthracene (DMBA) induced cellular differentiation in mouse skin

Abstract

Stable and novel silymarin bearing nanostructured lipid carriers (NLC) were prepared using a hot high pressure homogenization process. Silymarin NLC were physicochemically characterized via particle size, zeta potential, transmission electron microscope (TEM), entrapment efficiency (EE), in vitro release studies and optimized through experimental design. Stability data confirmed a stable dosage form. The anti proliferative activity of silymarin NLC was studied in 7,12-dimethylbenz[a]anthracene (DMBA) induced cellular progression/differentiation in an albino mice model using western blot and reverse transcription polymerase chain reaction (RT-PCR) analysis. In order to see the molecular changes with cellular proliferative controls such asornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), cyclooxygenase-2 (COX-2) and cyclin D1 at protein and messenger ribonucleic acid (mRNA) level were studied. The proliferation markers such as ODC, COX-2, cyclin D1 displayed reduced levels. In conclusion, silymarin NLC possessed activities against progression and proliferation, which were associated with enhanced solubility and stability of silymarin and greater permeation into the affected cells. Silymarin NLC could therefore be useful for chemo preventive use in skin cancer, as a topical formulation.