Novel double nanoemulsion loading of <i>Cordyceps militaris</i> extract: formulation, stability, <i>in vitro</i> digestion, and <i>in vivo</i> evaluation for regulation of acute lipid disorders

This study explores a novel approach for addressing acute lipid disorders using a double nanoemulsion system (NCMs) loading <i>Cordyceps militaris</i> extract. <i>Cordyceps militaris</i>, a medicinal mushroom, is valued for its bioactive compounds, particularly adenosine (ADE) and cordycepin (COR), which possess lipid-regulating properties. However, their limited stability and bioavailability present challenges. Therefore, this research focused on formulating a NCMs to enhance ADE and COR delivery. NCMs exhibited a mean droplet size of ∼102.8 nm with a PDI of 0.190 and a high encapsulation efficiency of over 90% for both ADE and COR. The <i>in vitro</i> stability of NCMs under simulated gastrointestinal conditions (SGF/SIF, varying temperature and pH) was confirmed, with a sustained release profile showing less than 15% release in SGF after 2 hours, followed by a marked increase in SIF, reaching approximately 75% release of ADE and 78% release of COR within 4 hours. Furthermore, the <i>ex vivo</i> efficacy of NCMs in modulating acute lipid disorders was assessed using a tyloxapol-induced hyperlipidemia mouse model. Results demonstrate that NCMs significantly reduced triglyceride levels (-75.67% reduction compared with the hyperlipidemic control, <i>p</i> < 0.05) and cholesterol (-45.45% reduction compared with the hyperlipidemic control, <i>p</i> < 0.05) in the tyloxapol-induced hyperlipidemia animal model. Results indicate the successful development of a stable, nano-sized NCMs, with promising <i>in vitro</i> release characteristics. The <i>in vivo</i> findings demonstrate the potential of the <i>Cordyceps militaris</i> extract-loaded NCMs to effectively regulate acute lipid imbalances. This study provides valuable insights into a functional food and a novel approach for managing lipid disorders, warranting future research in chronic models and clinical trials.