Preparation Of Curcumin-loaded Hemoglobin Nanoparticles With Enhanced Cellular Uptake, And Increased Bioactivity In Vitro And Bioavailability In Vivo

Curcumin possess a wide range of pharmacologica activities, especially anti-inflammatory and anti-tumor. However, its clinical usages are limited owing to its poor water solubility and low bioavailability. To solve this problem, we prepared novel curcumin-hemoglobin nanoparticles with a 14.4% drug loading, encapsulation efficiency of 75%and particle size of 81.8±3.3nm.Then, in vitro anti-tumor efficacy study of the novel curcumin-hemoglobin nanoparticles was conducted using MCF-7 and CACO-2 cell lines. Results showed that a significantly better anti-tumor efficacy could be obtained by curcumin-hemoglobin nanoparticles compared with the free curcumin. Following this, the cell uptake mechanism of curcumin-hemoglobin nanoparticles was further researched using sucrose, a typical clathrin- mediated endocytosis inhibitor. Results indicated that the cell uptake of the nanoparticles may dependent on the ATP-mediated clathrin endocytosis.Next, a preliminary study on the Oral dosage forms of curcumin-hemoglobin nanoprticles was conducted. The experiment was divided into two groups:free curcumin suspension (100mg/kg) and curcumin-hemoglobin nanoparticles (100mg/kg). Better drug uptakes of curcumin were obtained at different sampling time in curcumin-hemoglobin group compared with free curcumin suspension especially at 15min. The plasma concentration of curcumin-hemoglobin nanoparticles at 15min was 30 higher than the free curcumin suspension(592.9ng/ml vs 21.2ng/ml), showing a potent usage of hemoglobin as a drug carrier to enhance curcumin uptake.