5-Fluorouracil (5-FU) is a potent chemotherapeutic agent frequently used in combination therapy to treat diversified cancers. However, it possesses poor permeability and a short half-life. For the first time, the synthesis of gallic acid-stearyl amine (GA-SA) conjugate combined with 5-fluorouracil (5-FU) for the treatment of actinic keratosis in A431 human epidermal carcinoma cell line by the development of surface-modified liposome-based topical gel formulations for deeper skin penetration, higher retention in targeted site and reduction in systemic toxicity. The synergistic combination of 5-FU and GA–SA conjugate in a ratio of 1:1 (1 µg/mL: 10 µg/mL) (v/v) is effectively cytotoxic against the A431 cancer cells line. Still, it is safe against HaCaT normal cell line. Four different formulations were prepared by varying the soya lecithin and cholesterol viz. 9:1, 8:2, 7:3 and 6:4 respectively. The 5-FU bearing liposomal gel was prepared, and it was then subjected for characterization to determine parameters like viscosity, spreadability, pH, and drug content. In ex-vivo skin permeation, the flux and skin deposition were determined and compared with the marketed formulation. The results of cytotoxicity activity indicate that optimized gel formulation possesses the anti-cell proliferation activity of 50% better than the plain 5-FU drug. The ability of the vesicle preparation to deposit skin was further confirmed by confocal laser scanning microscopy. The gamma scintigraphy images demonstrated that significant radioactivity was noted in the targeted area (skin) for the liposomal gel compared to the marketed one, following our distribution studies.
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