Porous Baicalin-Fe(III) ICP@Propofol nanocomposites for enhanced anesthetic efficacy and reduced toxicity via neuroprotection and ultrasound assistance

To enhance the anesthetic efficacy of propofol while mitigating its systemic toxicity and irreversible developmental neurotoxicity, we developed a strategy leveraging the neuroprotective effects of baicalin in combination with propofol anesthesia via baicalin-based nanocomposites. High propofol-loaded porous Baicalin-Fe(III) infinite coordination polymer@propofol nanocomposites were synthesized, wherein baicalin coordinates with Fe³⁺ ions to form porous nanoparticles that encapsulate propofol within a core-shell structure. These nanocomposites exhibited an average diameter of 92.3 ± 10.2 nm and a pore volume of 0.322 cm³/g, achieving ultra-high propofol loading (∼62%) with no detectable leakage over 100 d, attributed to their large surface area and strong molecular interactions. When combined with focused ultrasound (FUS) and microbubbles, the effective dose (ED₅₀) of propofol decreased from 10 to 4.3 mg/kg, doubling the duration of anesthesia and extending the therapeutic window by 200%. Importantly, the therapeutic index improved 1.66-fold while vital physiological parameters remained stable. Histological analyses revealed an 80% reduction in neuronal injury compared to free propofol, and behavioral tests demonstrated significant enhancements in motor and cognitive performance, alongside recovery from propofol-induced irreversible developmental neurotoxicity, indicating effective neuroprotection. Collectively, this baicalin-propofol nanocomposite, coupled with FUS-mediated delivery, represents a promising approach for safe and long-term anesthesia in clinical applications.