Enhancement of in-vitro anti-oral cancer activities of silymarin using dispersion of nanostructured lipid carrier in mucoadhesive in-situ gel

Silymarin (SME) shows multiple therapeutic actions against several cancers, however, low aqueous solubility and poor bioavailability issues restrict its clinical use. In this study, SME was loaded in nanostructured lipid carriers (NLCs) and further incorporated in mucoadhesive in-situ gel (SME-NLCs-Plx/CP-ISG) for localized treatment of oral cancer. Using a 3³ Box-Behnken design (BBD), an optimized SME-NLC formula was developed with the ratios of solid lipids, surfactant concentration, and sonication time as independent variables, while particle size (PS), polydispersity index (PDI), and % encapsulation efficiency (EE) as dependent variables, resulting in 315.5 ± 0.1 nm PS, 0.341 ± 0.01 PDI, and 71.05 ± 0.05 % EE. Structural studies confirmed the formation of SME-NLCs. SME-NLCs incorporated in-situ gel demonstrated a sustained release for SME, indicating enhanced retention on the buccal mucosal membrane. The in-situ gel containing SME-NLCs showed a marked decrease in IC₅₀ value (24.90 ± 0.45 µM) than SME-NLCs (28.40 ± 0.89 µM) and plain SME (36.60 ± 0.26 µM). The studies demonstrated that Reactive oxygen species (ROS) generation potential and SME-NLCs-Plx/CP-ISG induced apoptosis at Sub-G0 phase owing to higher penetration of SME-NLCs led to higher inhibition against human KB oral cancer cells. Therefore, SME-NLCs-Plx/CP-ISG can be the alternative to chemotherapy and surgery with site-specific delivery of SME to oral cancer patients.

Excipients used in this study beside other: Migylol 812 N, Tween 80, Compritol 888, Carbopol 934P, Kolliphor P 407

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Meghanath B. Shete, Ashwini S. Deshpande, Pravin Shende, Enhancement of in-vitro anti-oral cancer activities of silymarin using dispersion of nanostructured lipid carrier in mucoadhesive in-situ gel, International Journal of Pharmaceutics, Volume 636, 2023, 122860, ISSN 0378-5173,
https://doi.org/10.1016/j.ijpharm.2023.122860.