Biopharmaceutical characterization of Ajwain (Carum copticum) seed extract-loaded self-microemulsifying drug delivery system for enhanced hepatoprotective and nephroprotective activity

The increasing demand for plant-based therapies has highlighted the need for innovative delivery technologies to enhance the bioavailability of phytoconstituents. Ajwain (Carum copticum) is a medicinal plant recognized for its antioxidant, anti-inflammatory, and hepatoprotective attributes. Nevertheless, its therapeutic application is greatly affected by insufficient aqueous solubility and low absorption. Targeting the biopharmaceutical performance improvement of Ajwain seed extract (ASE) by integrating it into a self-microemulsifying drug delivery system (SMEDDS) was considered, along with assessing its protective effects. ASE underwent GC-MS analysis for phytochemical profiling, followed by solubility assessment in several oils, surfactants, and co-surfactants. The improved SMEDDS-ASE was characterized physicochemically for micelle formation potential, dispersibility, gastrointestinal stability, and polymer miscibility with ASE. The hepatorenal protective effects were evaluated in a rat model of acute hepatorenal injury generated by cisplatin (7.5 mg/kg, i.p.) through the assessment of serum biomarkers and histological analysis. SMEDDS-ASE exhibited the formation of tiny micelles with an average droplet size of 183 ± 5.8 nm in water, resulting in a dispersibility enhancement of at least 2.4 times compared to ASE in water. The treatment of SMEDDS-ASE (75 mg/kg and 150 mg/kg, p.o.) significantly reduces different serum biomarker levels (decreased ALT, AST, ALP; p < 0.01; reduced creatinine, BUN; p < 0.05), which is ascribed to improved hepatorenal protection in a dose-dependent manner compared to ASE. Histological examinations suggest that SMEDDS-ASE may initiate the protection of hepatic and renal cells against damage and inflammation, thereby offering benefits in preventing diseases associated with free radicals. These findings suggest that the prospective implementation of the SMEDDS-based method may effectively enhance ASE's nutraceutical properties.