The current work highlighted the preparation method of Tanshinone IIA, Glycyrrhetinic acid Emulsion with eutectic (GT-eEmu) and investigated its effectiveness in the internal and external treatment of psoriasis.
Materials & methods
The optimal prescription ratios of the emulsions were screened based on single-factor and orthogonal experiments, in which the appearance, particle size, centrifugal stability, and placement stability of the emulsion were used as indicators. On this basis, the maximum drugs loading was determined and optimized by D-optimal. Then the gloss, consistency, uniformity, spreading, and centrifugal stability of the emulsion gel were used as indicators to screen the best preparation method of the emulsion gel. The gastrointestinal stability of GT-eEmu and the original drug was evaulated by the artificial gastrointestinal fluid test, while the irritation to the the gastrointestinal mucosa was investigated after treatment. In addition, the skin permeability and skin side effects of the preparation were studied. Finally, the therapeutic effects of various preparations on psoriasis in mice were studied based on PASI scores, HE pathological sections and the expression of SOCS1 and STAT3.
Results
The best optimized prescription of GT-eEmu was: oil phase 7%, emulsifier 4.5%, and emulsification temperature 60 ℃, where the drug loading of TSN IIA and GA were 0.17 and 0.70 g·L- 1. The best preparation method for GT-eEmu-Gel was to add carbomer 980 with 6% gel matrix to the emulsion prepared by the optimized method, followed by mixing with triethanolamine and adjusting the pH to 6.0-7.0 to prepare a 0.5% carbomer matrix emulsion. The gastrointestinal stability experiment showed that the addition of eutectic ingredients did not cause significant irritation to the gastrointestinal tract, while the good permeability and sustained release of GT-eEmu-Gel were shown by in vitro release assays and the emulsion gel form could further reduce the irritation of eutectic to the skin. Finally, imiquimod-induced psoriasis animal model experiments indicated that GT-eEmu and its gel could reduce the degree of skin lesions and histopathological changes in model mice, and decrease the average expression of SOCS1 and STAT3, which indicated these preparation had therapeutic effects on psoriasis. Additionally, the "internal and external treatment" group had the best effect compared with the oral-only group, while there was a significant difference (P < 0.01) compared with the model group.
Conclusion
The preparation process of GT-eEmu and GT-eEmu-Gel is stable and quality-controlled, which can improve the oral bioavail ability of both drugs to different degrees and reduce the irritation to the skin. The results showed that they have certain therapeutic effects on psoriasi, which can be safely administered orally and applied externally on the skin. At the same time, compared with the single treatment, the "internal and external combined treatment" method was the most effective, which indicates the concept of "internal and external combined treatment" method has practical significance.
