Sanguinarine has a history of use in both
folk medicine and early dermatology for the treatment of cutaneous
neoplasms. Applied indiscriminately, bloodroot is an escharotic agent with potential to cause extensive tissue
necrosis. However, when used in a controlled fashion,
sanguinarine imparts selective cytotoxic/anti-proliferative activity through multiple mechanisms against human/ murine
melanoma. To exploit
sanguinarine's observed activity against
melanoma, a targeted delivery system is required. We present a
sol-gel based nanoparticulate platform for encapsulating
sanguinarine chloride(sang-np)-a targeted therapeutic capable of steady, reliable delivery of predictable quantities of
drug over a sustained time period with minimal undesirable effects. Size and release kinetics of sang-np were characterized using dynamic light scattering and ultraviolet-visible spectroscopy respectively. In vitro efficacy of sang-np was assessed. At both 2 and 24 hours, free
sanguinarine killed > 90% of
B16 melanoma cells, assessed via MTT assay. At 2 hours, sang-np killed a portion of
melanoma cells, increasing to percentages comparable to free
sanguinarine by 24 hours. Control(empty) nanoparticles exerted minimal toxicity to
melanoma cells at both time points. TUNEL assay revealed that treatment with both
sanguinarine and sang-np induces apoptosis in
B16 melanoma cells, suggesting that both treatments act via the same mechanism of action. These data confirm controlled release of
sanguinarine from sang-np, as well as comparable efficacy and mechanism of action to
sanguinarine alone. This suggests that nanoparticle delivery of
sanguinarine may be a unique approach to capitalize on this potent agent's inherent anti-
tumor activity and overcome many of the limitations with its current formulation.