Enhancement in the Transdermal and Localized Delivery of Honokiol Through Breast Tissue

Honokiol is a natural phenolic anti-cancer compound isolated from an extract of seed cones from Magnolia grandiflora. This study investigated the transdermal delivery of honokiol using various enhancement methods and to explore the potential of honokiol to treat breast cancer directly via delivery through mammary papilla. Poration of dermatomed human skin with microneedles significantly increased the delivery of honokiol by nearly 3-fold (97.81 ± 18.96 μg/cm²) compared with passive delivery (32.56 ± 5.67 μg/cm²). Oleic acid was found to be the best chemical penetration enhancer, increasing the delivery almost 27-fold (868.06 ± 100.91 μg/cm²). Addition of oleic acid also resulted in better retention of drug in the porcine mammary papilla (965.41 ± 80.26 μg/cm²) compared with breast skin (294.16 ± 8.49 μg/cm²). Anti-cancer effect of honokiol was demonstrated with the decrease in the release of cytokine IL-6 and further suppression of Ki-67 proliferative protein. In addition, the topical honokiol formulation investigated was found to be safe and non-irritant. In summary, both microneedles and chemical enhancers can improve the absorption of honokiol through skin. Directly applying honokiol on mammary papilla is a potential administration route which can increase localized delivery into breast tissue.