Studies On Curcumin Loaded Polybutylcyanoacrylate Nanoparticles

Curcumin (CUR) is a polyphenol ingredient that has a variety of biological activities and pharmacological actions, such as anticancer, antioxidation, anti-inflammation, anti-bacteria, anti-virus. Recent studies have shown that CUR can block brain tumor formation, have a potential role in curing Alzheimer's disease and Parkinson's disease, protect the brain against various oxidative stressors and prevent cognitive deficits. However, due to the presence of blood-brain barrier (BBB), it is hard for CUR to enter brain. In addition, the poor absorption and low bioavailability of curcumin because of the insolubility of curcumin limit its clinical application.Polybutylcryanoacrylate nanoparticles (PBCN) are a type of nano-drug delivery system with biodegradable and compatible polymer material as drug carrier. PBCN coated with surfactants can deliver drug across BBB, moreover, the system can effectively control the release of drug, improve the oral bioavailability and be applied to various administration routs.PBCN were prepared with curcumin as model drug in this study. The amount of curcumin delivered by PBCN through BBB was investigated by bio-distribution in mice. The possibility of PBCN as oral delivery carrier of curcumin was evaluated by the study of pharmacokinetics, the absorption mechanism and absorption segment in rats.The method of "emulsification polymerazation" was used to prepare PBCN loaded curcumin (CUR-PBCN). The effects of different factors such as surfancts, polymers, pH, the time and temperature of emulsification, the time and speed of stirring on the formation of PBCN were studied. Moreover, the orthogonal experimental design was applied to optimize the formulation with the morphous, and drug loading of CUR-PBCN based on the main factors including surfactants, polymers and pH. As a result, the optimized nanoparticles were spherically shaped under the transmission electron microscope, and the particle size was between 50 nm and 200 nm, the mean drug loading was 2.63%, which attained the predicted objective.The dialytic method was used to study the release of CUR from CUR-PBCN in vitro and the curve fitting method was used to find the drug release equation. The results showed that the release of CUR from CUR-PBCN in vitro fitted double phase kinetics model well. The equation was as follows:100-Q= 73.46 e-0.1703t+ 27.72e"0.0052t (R0=0.9518, Rβ=0.9877). CUR-PBCN had an initial fast release followed by slow release compared to crude CUR solution.The concentration of CUR was examined by the HPLC in the pharmacokinetic experiment of CUR-PBCN in mice with CUR solution as control. Program DAS 2.0 was applied to calculate pharmacokinetic parameters. The results showed that the processes in rat of CUR solution and CUR-PBCN via intravenous injection fitted two-compartment model,however, via oral administration, the process of CUR-PBCN fitted two-compartment model while single-compartment model for the CUR suspension. The AUC of CUR-PBCN via intravenous injection was 1.6-fold that of CUR solution. Tissue distribution study in mice via intravenous injection indicated that the distribution of CUR in tissue was greatly changed due to the encapsulation of PBCN, and higher CUR levels in heart, liver, lung, kidney and brain were obtained for CUR-PBCN formulation compared with the CUR solution. The relative bioavailability of CUR-PBCN to crude CUR suspension after oral administration was about 833.5%.The intestinal absorption kinetics of CUR-PBCN with low, middle, high concentrations at the gastrointestinal tract was investigated in rats with in situ perfusion method. The results indicated that the absorption indexes(Ka) for CUR-PBCN with low, middle, high concentrations were (0.091±0.013) h-1,(0.099±0.009) h-1 and (0.101±0.021) h-1, respectively, and the absorption principal mechanism for CUR-PBCN in intestine conformed to passive diffusion. The study on main absorption segment showed that CUR-PBCN could be absorbed in all the segments of the intestine, and the absorption percentages of duodenum, jejunum, ileum and colonic were (26.12±1.55)%, (22.38±2.51)%, (40.40±3.64)%, (45.43± 3.09)%, respectively. The main segments of CUR-PBCN absorbed in intestine were ileum and colonic.In this dissertation it was proved that PBCN coated with tween 80 could significantly enhance the amount of insoluble drug in brain and indeed increased the absorption of poorly soluble drugs after oral administration. Thus, it is a new drug delivery system with great investigating value and potential.