We disclose microemulsions (ME) of curcumin (CUR) with docosahexaenoic acid (DHA)-rich oil (CUR DHA ME) for targeted delivery to the brain. MEs of CUR (5 mg/mL) with and without DHArich oil (CUR Capmul ME) suitable for intravenous and intranasal administration exhibited negative zeta potential, globule size 520 nm and good stability. Following intravenous delivery MEs exhibited high brain concentration with CUR DHA ME exhibiting a 2.8-fold higher C max than CUR solution. Furthermore, high and sustained concentration was demonstrated even at 24 h, which was 8-and 2-fold higher than CUR solution and CUR Capmul ME, respectively. Brain concentrations following intranasal administration were, however, substantially higher as evident from higher C max and AUC and sustained compared to corresponding intravenous formulations signifying nose to brain targeting. The high brain concentration of CUR DHA ME is ascribed to the targeting efficiency enabled by DHA-mediated transport across the blood-brain barrier (BBB). Histopathological and nasal toxicity confirmed safety of the MEs. Concentrationdependent cytotoxicity in vitro, on human glioblastoma U-87MG cell line was observed with CUR DHA MEs and with the blank DHA ME, implying anticancer potential of DHA. The dramatically low IC 50 value of CUR DHA ME (3.755 ± 0.24 ng/mL) is therefore attributed to the synergistic effect of CUR and DHA in the ME. The CUR concentration achieved with CUR DHA ME at 24 h which translated to 466-fold(intranasal) and 421-fold (intravenous) the IC 50 value in the U-87MG cell line suggests great promise of CUR DHA ME for therapy of brain cancer by both routes.
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