Quercetin (QC) is a typical plant flavonoid, possesses diverse pharmacologic effects including antiinflammatory, antioxidant, anti-cancer, anti-anaphylaxis effects and against aging. However, the application of QC in pharmaceutical field is limited due to its poor solubility, low bioavailability, poor permeability and instability. To improve the bioavailability of QC, numerous approaches have been undertaken, involving the use of promising drug delivery systems such as inclusion complexes, liposomes, nanoparticles or micelles, which appear to provide higher solubility and bioavailability. Enhanced bioavailability of QC in the near future is likely to bring this product to the forefront of therapeutic agents for treatment of human disease.

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Purpose This study aimed to develop a novel methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelle drug delivery system to improve lamotrigine (LTG) distribution in the hippocampus. Methods LTG-loaded mPEG-PLA/TPGS mixed micelles and LTG-loaded mPEG-PLA micelles were formulated, and their characteristics, particle size, surface morphology, and release behavior in vitro were researched. Then, a microdialysis sampling technique coupled with two validated chromatographic systems was developed for the continuous measurement of the protein-unbound form of LTG in the rat plasma and hippocampus after administering two kinds of micelles and LTG solution intranasally. Results The drug loading and mean size of LTG-loaded micelles and LTG-loaded mixed micelles prepared with optimal formulation were 36.44%±0.14%, 39.28%±0.26%, 122.9, and 183.5 nm, respectively, with a core–shell structure. The cumulative release rate in vivo of LTG-loaded mixed micelles was 84.21% at 24 hours and showed more sustained release while that of LTG-loaded micelles was 80.61% at 6 hours. The T max and area under concentration-time curve from zero to time of last quantifiable concentration of LTG solution, LTG-loaded micelles, and LTG-loaded mixed micelles were 55, 35, and 15 minutes and about 5,384, 16,500, and 25,245 (min⋅μg)/L in the hippocampus, respectively. Conclusion The results revealed that LTG-loaded mPEG-PLA/TPGS mixed micelles enhanced the absorption of LTG at the nasal cavity and reduced the efflux of LTG in the brain, suggesting that the function of TPGS inhibited P-glycoprotein and LTG-loaded mPEG-PLA/TPGS mixed micelles had the potential to overcome refractory epilepsy.