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Curcumin, the main bioactive component of turmeric, has a wild range of beneficial effects on central nervous diseases, including anti-Alzheimer’s disease, antioxidant stress, and anti-inflammation. Currently, it has been demonstrated the anti-epileptic potential. However, curcumin has poor water solubility, high sensitivity to light and heat, and low absorption, which results in low bioavailability and greatly limits the clinical application of curcumin, as well as the elusive effects in anti-epileptic treatment.This study aimed to develop a curcumin hydroxypropyl-β-cyclodextrin inclusion complex (CUR-HP-β-CD) to improve its bioavailability and facilitate its potential development as an anti-epileptic drug. The CUR-HP-β-CD was generated by the solvent evaporation method, which has efficient entrapment, high solubility, and facilitated bioavailability and brain distribution.The solubility of the CUR-HP-β-CD was 63.5, 60.1, and 52.9 times that of the unformulated curcumin in H 2 O, HCl (pH 1.2), and PBS (pH 6.8), respectively. The bioavailability of CUR-HP-β-CD is improved 2.8 times and 38.7 folds higher brain concentrations. Moreover, the therapeutic anti-epileptic effects of CUR-HP-β-CD were much more effective in pentylenetetrazol (PTZ)-induced zebrafish and mouse models.This study showed a simple and reproducible strategy to effectively improve the bioavailability and therapeutic effects of curcumin, which could be potentially used in epilepsy treatment. Curcumin, the main bioactive component of turmeric, has a wild range of beneficial effects on central nervous diseases, including anti-Alzheimer’s disease, antioxidant stress, and anti-inflammation. Currently, it has been demonstrated the anti-epileptic potential. However, curcumin has poor water solubility, high sensitivity to light and heat, and low absorption, which results in low bioavailability and greatly limits the clinical application of curcumin, as well as the elusive effects in anti-epileptic treatment. This study aimed to develop a curcumin hydroxypropyl-β-cyclodextrin inclusion complex (CUR-HP-β-CD) to improve its bioavailability and facilitate its potential development as an anti-epileptic drug. The CUR-HP-β-CD was generated by the solvent evaporation method, which has efficient entrapment, high solubility, and facilitated bioavailability and brain distribution. The solubility of the CUR-HP-β-CD was 63.5, 60.1, and 52.9 times that of the unformulated curcumin in H 2 O, HCl (pH 1.2), and PBS (pH 6.8), respectively. The bioavailability of CUR-HP-β-CD is improved 2.8 times and 38.7 folds higher brain concentrations. Moreover, the therapeutic anti-epileptic effects of CUR-HP-β-CD were much more effective in pentylenetetrazol (PTZ)-induced zebrafish and mouse models. This study showed a simple and reproducible strategy to effectively improve the bioavailability and therapeutic effects of curcumin, which could be potentially used in epilepsy treatment.

Curcumin-loaded hydroxypropyl-β-cyclodextrin inclusion complex with enhanced dissolution and oral bioavailability for epilepsy treatment