The present study aimed to develop and evaluate various lyotropic liquid crystals (LLCs) loaded with doxorubicin
(DOX) as transdermal drug delivery systems for the potential treatment of breast cancer. The pseudo-ternary
phase diagram was constructed using fish oil and oleic acid, Tween 80, ethyl alcohol or glycerin, and water
to identify the region of LLCs. The microstructure of the selected LLCs was confirmed using polarized light
microscopy showing lamellar and hexagonal shapes. The selected LLCs exhibited promising characteristics, as
evidenced by their rheological behavior, pH, drug-loading capacity, and in vitro sustained drug release. Additionally,
their ex vivo skin permeation and deposition studies revealed up to 1.4- and 7-fold increases in the
permeability and skin deposition of DOX-loaded LLCs, respectively, when compared with DOX solution. Moreover,
enhanced permeability and deposition were confirmed by examining rat skin using confocal laser microscopy.
In the in vitro cytotoxicity study, DOX-loaded LLCs showed significantly higher activity against MCF-7 cell
lines (showing up to a 70-fold increase) when compared with DOX solution. Finally, the skin sensitivity study
indicated that LLCs have good skin safety and tolerability. Our findings indicate that LLCs have significant potential
as a transdermal drug delivery system for the management of breast cancer.