Formulation and Optimization of Neomycin Sulfate–Thioctic Acid Loaded in a Eucalyptus Oil Self-Nanoemulsion to Enhance the Beneficial Activity of the Substances and Limit the Side Effects Associated with the Treatment of Hepatic Coma

Abstract In patients suffering liver damage, the gut microbiota and their metabolic products are reported to be the key factors in the worsening of associated psychiatric and neurological conditions. In particular, the increased production of ammonia resulting from microbial activities in the gut is considered one of the important factors that lead to the development of hepatic coma. The use of neomycin, an antimicrobial that has been approved by the United States Food and Drug Administration, in the treatment of hepatic coma is restricted because its therapeutic use is often accompanied by severe toxicities (e.g., nephrotoxicity). The present study aims to optimize the development of a neomycin-loaded self-nanoemulsifying drug delivery system using a statistical design into which thioctic acid is incorporated (NM-TH-SNEDDS). Thioctic acid has a well-established antioxidant efficacy, which in turn reduces the nephrotoxic effect of neomycin in patients, and also has a significant hepatoprotective role. The Box–Behnken design of statistical analysis was performed to optimize the formulations. The optimized formula showed 150 nm globule size, 592 μg of thioctic acid permeated, microbiological activities enhanced 12 times, and ameliorative properties of the formulation in terms of renal function parameters were enhanced according to the results of serum creatinine measurement. Overall, it could be concluded that the NM-TH-SNEDDS formulated using eucalyptus oil would be a suitable platform for the treatment of hepatic coma, with enhanced efficacy and safety. The findings of the present study need to be explored in detail to gain further insights that could influence the direction of future clinical research.