Preparation and evaluation of gastrodin-ferulic acid co-loaded liposome gel patches for the treatment of migraine

Gastrodin (GA) and ferulic acid (FA) are the main active ingredients of the traditional Chinese medicine Da Chuan Xiong formula for migraine treatment. This study aimed to develop a gastrodin-ferulic acid co-loaded liposomal gel patch (GA/FA-Lip-GelP) as a transdermal drug delivery system (TDDS) for migraine management. TDDS overcomes the limitations of first-pass metabolism associated with oral administration and is particularly suitable for migraine patients experiencing nausea and vomiting. The system contains three key components: sodium polyacrylate (hydrophilic gel matrix), laurocapram (Azone, permeation enhancer), and GA/FA-loaded liposomes (nanocarrier). This combination enables effective systemic drug delivery. The GA/FA-Lip was prepared using central composite design optimization. Subsequently, the GA/FA-Lip-GelP formulation was developed through single-factor screening and Box-Behnken designs. The optimized GA/FA-Lip-GelP was systematically evaluated via in vitro release studies, ex vivo transdermal permeation experiments, and in vivo pharmacokinetic/pharmacodynamic analyses. The GA/FA-Lip was prepared via thin-film dispersion, forming uniform spherical nanoparticles (146.34 ± 1.35 nm). These nanoparticles achieved high encapsulation efficiencies (GA: 85.26 ± 1.90%; FA: 86.92 ± 2.23%) and demonstrated excellent stability. The final GA/FA-Lip-GelP demonstrated optimal adhesion, sustained drug release, and content uniformity under low-temperature storage. Compared to oral administration and non-liposomal gel patches, GA/FA-Lip-GelP showed significantly enhanced transdermal permeation, improved pharmacokinetic profiles, and superior therapeutic efficacy. GA/FA-Lip-GelP demonstrated potential as an effective migraine treatment by overcoming first-pass metabolism, thereby improving bioavailability and enabling sustained drug release.