| Nitidine Chloride(NC)is one of the alkaloids isolated from the root of Zanthoxylum nitidum(Roxb.).DC. Our previous study showed that NC could inhibit the tumor. Meanwhile, it could kill natural cell. Solid lipid nanoparticles (SLN) is a promising drug delivery system with Solid lipid as drug carriers, particle diameters ranging between 50 and 1000nm, which has the advantages of high physical stability, slow speed of drug leakage and good targeting property, etc. To make the most use of the anti-tumor activity, improve targeting property, in the study, we study on the NC-SLN with nitidine chloride(NC) as a model drug.Objective1. To study the preparation and quality evaluation of NC-SLN.2. To explore the pharmacokinetics rule of NC-SLN in rats, work out and analyze the pharmacokinetic parameters.3. To study the distribution rule of NC-SLN in rats, and evalute the targeting property.4. To investigate the anti-HepG-2 tumor activity of NC-SLN in nude mice.Methods1. NC-SLN were prepared by high-pressure homogenization. Moreover, a freeze-dried method was investigated in order to improve the stability of the NC-SLN solution. It`s morphology, particle diameters, pH, entrapment efficiency and drug loading , stability were studied.2. NC-SLN and NC were intravenously administrated to rats, the concentration-time dates of NC in plasma samples were determined by HPLC, and the pharmacokinetic parameters were calculated and analyzed by means of SPSS software.3. NC-SLN and NC were intravenously administrated to rats, the drug concentrations of heart, liver, spleen, lung, kidney and brain were determined by the HPLC at various times, and evaluate the targeting property of NC-SLN.4. The models of nude mice with human hepatocellular transplanted tumor were established. The anti-tumor activity was surveyed by tumor inhibitive ratio(IR).Results1. The shape of NC-SLN was spherical, narrowly-distributed, And well distributed with a mean diameter of (237±5.6)nm, PDI=(0.217±0.004), pH close to (5.18±0.13), an entrapment efficiency of (77.40±1.09)%, a drug loading of (4.13±0.16)%, and good stability.2. The main parameters of NC were T1/2=(163.519±9.9019)min, AUC(0-t480)=(41.8383±1.302)μg·mL-1·min, AUC(0-∞)=(49.1851±2.3818)μg·m- L-1·min, MRT=(235.9582±14.2884)min, Cl(s)=(0.2037±0.0100)L·kg-1·min-1, Vss =(47.9598±1.2787)L·kg-1; The main parameters of NC-SLN were T1/2=(27 6.9393±7.9606)min, AUC(0-t480)=(120.6072±1.926)μg·mL-1·min, AUC(0-∞) =(167.0805±3.2012)μg·mL-1·min, MRT=(399.6239±11.4873)min, Cl(s)=(0.05 99±0.0011)L·kg-1·min-1, Vss=(23.9177±0.4930)L·kg-1.3. NC-SLN were mainly distributed in liver, lung, while decrease in heart and brain. The Re,R%T,Ce of liver were higher than others, it indicted that the NC-SLN improve the liver targeting property.4. In nude mice anti-tumor assay indicated that the NC-SLN IR with 58.87% against HepG-2, It was stronger than NC.Conclusion1. The NC-SLN can be prepared by high-pressure homogenization has small size, high encapsulation efficiency and good stability.2. Compare with the NC, NC-SLN show the longer T1/2, higer AUC(0-∞) and MRT, lower Cl(s), it indicate that the NC-SLN contain characteristic of sustained-release.3. NC-SLN show a good liver targeting property in vivo, which may improve it`s activity, decrease doses of NC .4. NC-SLN has great anti-HepG-2 tumor activity.
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