Fatty acid-arginine vesicles with prominent encapsulation efficiency and substantial transdermal delivery of sinomenine hydrochloride

In clinical practice, sinomenine hydrochloride (SH) is a valuable and promising medication for rheumatoid arthritis. However, oral administration of SH is less bioavailable with adverse reactions to the digestive system, blood circulation, and nervous system, among which rash, gastric ulcer, gastric haemorrhage and anaphylactic shock are the most common. Owing to a short half-life in the human body (0.791 h), patient compliance is greatly reduced, resulting in frequent administration for patient treatment. Therefore, SH encapsulated in vesicles with amphiphilic layers would be more stable and have fewer side effects. In this study, a transdermal drug delivery system (TDDS) for SH was designed utilizing fatty acid vesicles as carriers. The physicochemical properties and aggregate morphology of two carriers: arginine-oleic acid ([Arg][Ole]) and arginine-decanoic acid ([Arg][Dec]) were investigated, and the SH encapsulation method by the above materials was optimized and verified by single factor and central composite design (CCD) response surface methods. Notably, the encapsulation efficiency (EE) of SH in [Arg][Dec] vesicles was increased to 83.5 % and the centrifugal stability (CS) to 90.4 %. Moreover, as a result of the Conductor-like screening model for real solvents (COSMO-RS) calculation, it was found that the interaction between [Arg][Dec] and SH was stronger than that of [Arg][Ole], aligning with experimental results. In comparison to the sustained release period in water, the in vitro release experiment showed that the [Arg][Ole] and [Arg][Dec] vesicles could be prolonged to 17 hours. Importantly, the cumulative skin permeability of [Arg][Dec] vesicles reached 1665.59 μg·cm−2 after 48 h, which is much higher than the previous literature value of around 663 μg·cm−2. These results suggest that vesicles provide a viable method for transdermal delivery of SH.