Physicochemical and biomolecular characterisation of plumbagin incorporated thermoresponsive nanoformulation
摘要
Cervical cancer is the second leading cause of death in women globally. Current treatments are associated with adverse effects, underscoring the need for novel anticancer formulations to improve efficacy and targeted drug delivery. Plumbagin, a bioactive naphthoquinone with potent anticancer and pro-apoptotic properties, was selected as a promising therapeutic candidate for cervical cancer. Accordingly, four plumbagin-loaded nanoformulations (F1, F2, F3, and F4) were fabricated by ionotropic gelation technique and was evaluated for LCST behavior and drug release profiles. The optimized formulation was evaluated in LPS-induced inflammation in SiHa cells for its effects on cell migration, apoptosis, autophagy, cell cycle progression, and cancer-related gene expression. Nanoformulations exhibited thermoresponsive properties in both normal (37 °C) and diseased conditions (39 °C) with LCST between 30 and 40 °C. Among them, F3 showed superior controlled drug release, achieving 54.3% and 31.7% release at 37 °C and 39 °C, respectively, through diffusion as described by the Higuchi model. Consequently, F3 was evaluated for anticancer activity in LPS-induced SiHa cells at 0.25, 0.75, and 1.5 µg/mL. The 0.75 µg/mL dose demonstrated significant anticancer effects, including inhibition of cell migration, induction of apoptosis and autophagy, and G2/M phase cell-cycle arrest, as confirmed by fluorescence staining and flow cytometry. These effects were further substantiated by increased expression of BAX, Beclin and LC3 decreased expression of BCL2, CDK1, Cyclin B1 and activation of caspase-9, confirming the induction of apoptosis. The prepared thermoresponsive nanoformulation with anticancer potential can be an effective alternative for treating and managing cervical cancers. However, further studies are warranted.
Graphical Abstract