Docosahexaenoic acid-mediated, targeted and sustained brain delivery of curcumin microemulsion.
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 DHA-rich oil (CUR Capmul ME) suitable for intravenous and intranasal administration exhibited negative zeta potential, globule size  <20 nm and good stability. Following intravenous delivery MEs exhibited high brain concentration with CUR DHA ME exhibiting a 2.8-fold higher Cmaxthan 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 Cmaxand 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. Concentration-dependent 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 IC50value 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  >66-fold(intranasal) and  >21-fold (intravenous) the IC50value in the U-87MG cell line suggests great promise of CUR DHA ME for therapy of brain cancer by both routes.
a Department of Pharmaceutical Sciences and Technology , Institute of Chemical Technology , Matunga , India Mumbai.
Rajshree L
RL
Shinde
a Department of Pharmaceutical Sciences and Technology , Institute of Chemical Technology , Matunga , India Mumbai.
Padma V
PV
Devarajan
D000281:Administration, Intranasal / Q000379:methods; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D001932:Brain Neoplasms; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D004281:Docosahexaenoic Acids / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000008:administration & dosage* / Q000737:chemistry; D005909:Glioblastoma / Q000188:drug therapy; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D003692:Delayed-Action Preparations; D004655:Emulsions; D004281:Docosahexaenoic Acids; D003474:Curcumin
Brain targeting; U-87 MG human glioblastoma cell line; curcumin microemulsion; docosahexaenoic acid; intranasal; intravenous