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Background: This study evaluates transdermal delivery of tamoxifen (TXN) as an alternative to the oral route of administration in treating breast cancer, which is the leading cause of cancer-related death in women globally. Oral TXN, a Class II drug, is associated with first-pass metabolism and serious side effects, including secondary cancers. Objectives: To enhance transdermal delivery, lipid-based transethosomes (TRS) were formulated using three different 24 factorial designs with various non-ionic surfactants, including Tween 20®, Span 20®, and Span 80®. Methods: Optimized TRS formulations were incorporated into HPMC-based gels and characterized for morphology, drug content, pH, viscosity, spreadability, ex vivo skin penetrat
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