Sesamol loaded transfersome gel for transdermal administration: novel approach for breast cancer therapy

BACKGROUND: Breast cancer remains a major global health burden, with existing treatment approaches facing challenges related to systemic toxicity, drug resistance and limited bioavailability. Sesamol, a natural antioxidant with anticancer potential, faces challenges of low skin permeability. Transfersomes offer a promising strategy to enhance transdermal delivery. The present study aimed to formulate and optimize a phospholipid-enriched sesamol-loaded transfersome (SM-TF) for breast cancer management. RESULTS: The optimized formulation (Opt-SM-TF) exhibited a vesicle size of 184.8 ± 3.4 nm with a polydispersity of 0.229 ± 0.01, as well as an entrapment efficiency of 90.23 ± 2.8% and zeta potential of -23.43 ± 2.80 mV. In vitro release studies demonstrated significantly higher drug release from Opt-SM-TF (82.08 ± 3.04%) compared to sesamol suspension (40.96 ± 2.09%) (P < 0.05). Antioxidant activity of Opt-SM-TF (79.65 ± 1.86%) surpassed that of sesamol solution (62.86 ± 1.52%) and was comparable to the reference standard ascorbic acid (88.40 ± 2.83%). Following incorporation into a Carbopol-based gel (Opt-SM-TFG), key parameters such as spreadability, extrudability, pH and texture were assessed. Ex vivo permeation and confocal studies demonstrated 2.2-folds higher permeation and deeper skin penetration (60 μm versus 20 μm) for Opt-SM-TFG compared to sesamol suspension gel (SM-SUSG) (P < 0.0001). In vitro cytotoxicity on MCF-7 (i.e. Michigan Cancer Foundation-7) breast cancer cells revealed significantly greater cytotoxic (P < 0.001) and a marked increase in superoxide dismutase activity (P < 0.001) for Opt-SM-TFG. Furthermore, levels pro-inflammatory cytokine (interleukin-2, interleukin-6 and tumor necrosis factor-α) were significantly downregulated in Opt-SM-TFG (P < 0.001 and P < 0.05). CONCLUSION: Opt-SM-TFG demonstrated superior skin permeation, antioxidant, anticancer and anti-inflammatory potential compared to suspension gel, highlighting its promise as an effective transdermal platform for breast cancer therapy, warranting further in vivo and clinical evaluation.