Preparation of a self-emulsifying nanoemulsion of Salvianolic acid A and its nephroprotective effects on doxorubicin-induced nephropathy

Background Doxorubicin-induced nephropathy has a poor prognosis, with limited treatment options. Salvianolic acid A (SAA) possesses anti-inflammatory effects; the oral application of SAA is hampered by its poor intestinal permeability, limiting its suitability for long-term therapy. Self-emulsifying drug delivery systems (SEDDS) offer an oral platform suitable for prolonged administration.Methods Excipients were screened through solubility testing; the formulation was optimized using a pseudo-ternary phase diagram combined with Star-point design and response surface methodology. In vitro, the cytotoxicity and cellular uptake of SAA-SEDDS were evaluated in podocytes, and the doxorubicin concentration for model establishment was determined by a dose–response assay. In vivo rat model of doxorubicin-induced nephropathy was established via two tail-vein injections of doxorubicin to evaluate the drug’s efficacy and biosafety.Results The optimized formulation had a particle size of 115 nm, an encapsulation efficiency of 87%, and a drug loading of 10.3% (w/w). In vitro experiments demonstrated that SAA-SEDDS exhibited acceptable biocompatibility, and semi-quantitative analysis suggested time-dependent internalization of C6-labeled SAA-SEDDS by podocytes. In vivo results indicated that SAA-SEDDS alleviated doxorubicin-induced nephropathy symptoms and exhibited acceptable short-term biosafety.Conclusion SAA-SEDDS may enhance the therapeutic efficacy of SAA and provide new evidence for the nanomedicine-based treatment of doxorubicin-induced nephropathy.