Studies On Curcumin Loaded Lipid Cubic Liquid Crystalline Nanoparticles

Curcumin, isolated from the rhizomes of Curcuma longa, is a natural phenolic compound which is used widely in food industry as pigment. In recent years, considerable research has shown its pharmacological activity in anti-cancer, anti-inflammatory, free radical scavenging, cholesterol lower, etc. However, owing to main drawbacks such as low solubility, instability, poor bioavailability, the clinical application of CUR is limited severely. Lipid cubic liquid crystalline nanoparticles, referred to as liquid crystalline nanoparticles (LCN), is an emerging drug delivery system. Its unique structure consists of bicontinuous lipid bilayer separating two networks of water channels. LCN may be used as water-insoluble drug carrier to enhance oral absorption and bioavailability. In this study, curcumin loaded liquid crystalline nanoparticles (CUR-LCN) was prepared, and the physical and chemical properties of CUR-LCN were described. Meanwhile, the oral absorption mechanism and site studies of CUR-LCN and the pharmacokinetics in rats were investigated.With drug loading and encapsulated efficacy as index, the CUR-LCN was prepared using hot, high-pressure homogenization in which the Single-factors, such as the amount of GMO, the amount of CUR, water volume, the ratio of GMO to F127, temperature, homogeneous pressure and shear dispersing time, were investigated, and then, the prescription and preparation process were further optimized via the uniform design test. The nanoparticles were spherical under transmission electron microscope with average particle size of176.1nm, zeta potential of-25.19mV, average drug loading of (1.5±0.2)%. In vitro release of CUR-LCN was evaluated using a dynamic dialysis method, and the results indicated that the cumulative release percentage was60%at36h, and the release equation was ln(1-Q)=-0.0251t-0.0075. The obtained CUR-LCN showed sustained release property compared to crude CUR.The absorption of CUR-LCN in the gastrointestinal tract was studied using in situ perfusion method in rats. It showed that the absorption percentage of CUR-LCN was (19.45±0.82)%after2h in stomach. The intestinal absorption kinetics of CUR-LCN with low, middle, high concentrations was investigated and the Ka values were0.1150h-1,0.1170h-1,0.1308h-1, respectively; t1/2values were6.03h,5.92h and5.30h, respectively. The liner manner between InX and t showed the principal mechanism for intestinal absorption of CUR-LCN was passive diffusion. The test of main segment indicated that CUR-LCN could be absorbed by all the segments of the intestine, and the absorption percentages of duodenum, jejunum, ileum and colonic were (27.10±6.02)%,(16.83±4.99)%,(26.05±8.16)%and (20.78±7.79)%, respectively. The main segments of CUR-LCN absorbed in intestine were duodenum and ileum.The pharmacokinetic experiment of CUR and CUR-LCN was carried in rats. The concentration of QT in plasma was detected by HPLC. Program DAS2.0was used to obtain pharmacokinetic parameters. The rats were administrated orally with CUR suspension (250mg/kg) and CUR-LCN (50mg/kg), respectively. The results showed that the pharmacokinetics processes of both preparations were all fitted one-compartment model. The absorption of CUR in CUR-LCN was markedly improved, and the relative bioavailability was395.56%compared to crude CUR.