Design-Expert® Optimization of Tamoxifen-Loaded Transethosomal Gels: A Promising Transdermal System with Cytotoxicity and Stability Validation.

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 penetration, and deposition. Additionally, cytotoxicity and stability were assessed.

Results

All TXN-TRS gels were suitable for transdermal use; however, Span 20®-based TRS gel demonstrated the highest skin penetration (40.3 ± 1.5 µg/cm2), representing a 127-fold enhancement rate compared with the non-ethosomal TXN gel. In line with the enhanced penetration profile, cellular studies on MCF-7 cells showed concentration-dependent cytotoxicity, reaching 91.24 ± 1.01% inhibition at 2% w/w after 72 h, with an IC50 value of 0.85 ± 0.02% w/w. Stability testing showed all formulations were more stable under refrigeration than at dry room temperature storage, supporting their potential as preclinical transdermal tamoxifen delivery platforms.

Conclusions

Span 20®-based TXN transethosomal gel markedly enhanced skin penetration while maintaining potent cytotoxic activity, supporting its further preclinical evaluation as a promising transdermal alternative to oral tamoxifen.