Study On Andrographolide Derivative ATC-Ⅱ Solid Lipid Nanoparticles Drug Delivery Systems

Andrographis paniculata(Burm.f.)Nees was found in India and planted in east, middlesouth and southwest China. It is used extensively as an antipyretic, anti-inflammtory and antivirus medicine for a long time. Recently, it’s newly pharmacological activities were found, such as immune activity, antitumor effect, hepatoprotective activity, inhibitory effect on platelet aggregation, antihypotensive effect, antifertility activity and antihyperglycemic effect, and the derivatives have strong anti-tumour effect too.hi the present study, ATC-Ⅱ loaded solid lipid nanoparticles(ATC-Ⅱ-SLN) using Compritol888ATO as material, poloxamer (F-68) as the emulsifier,was prepared by high pressure homogenization. ATC Ⅱ-SLN was expected to enhance oral bioavailability of ATC-Ⅱ and have a good targeting effect on liver. ATC-Ⅱ-SLN were studies in detail and systematically,including anti-tumor effect in-vitro, the physical and chemical characteristic, ATC Ⅱ-SLN characteristics,pharmacokinetic in rats and distribution in mice after oral administrationATC Ⅱ-SLN were prepared by cold-homogenization,To optimize the formulation of ATC-Ⅱ Solid Lipid Nanoparticles(ATC-Ⅱ-SLN) by central composite design-response surface. The influence factors such as drug carrier ratio, emulsifier concentration, homogeneousstress were investigated using entrapment efficiency,mean diameter and Zeta potential as evaluation parameters. Eventually established a formulation of preparation ATC-II-SLN (drug carrier ratio (A)9.0%, emulsifier concentration (B)1.5%and homogeneous pressure (C)55MPa), the ATC-Ⅱ-SLN encapsulation efficiency, particle size, zeta potential, respectively,95.55%,243.13nm,-33.5mV.By dialysis method to study ATC-II-SLN release mechanism in vitro. Release mechanism in line with Riger-Peppas equation, the diffusion index n=0.461, and ranged from0.43to0.85, indicating that the ATC-II-SLN release to conform to the non-the Fick’sdiffusion mechanisms, the diffusion of the drug and lipid skeleton dissolution a synergistic effect.To investigate oral bioavailability of ATC-Ⅱ-SLN in rat. Program3p97was applied To the calculation of pharmacokinetic parameters. the results show that the ATC-II-SLN in the pharmacokinetics of the process in line with the two compartment model, the main pharmacokinetic parameters showed that the Cmax, AUC, MRT, CLs were significant difference (P＜0.01), analysis of variance results show that the main source of error is SLN. To the formula: F%=AUCSLN/AUC×100, the calculation of ATC II-SLN relative bioavailability results of the ATC-II-SLN relative biological availability of579.1%.The mice were employed as experimental animal to study body distribution of ATC-Ⅱ-SLN afler oral administration. The results of student test and one-way analysis of variance showed that ATC-Ⅱ-SLN could distinctly change the distribution of ATC-Ⅱ in vivo and greatly increased the concentrations of ATC Ⅱ in liver in contrast to ATC-Ⅱ after p. o. Overall targeting efficiency(Te), targeting index(TI)and relative overall targeting efficiency(RTe)of ATC-Ⅱ-SLN was calculated and compared to ATC-Ⅱto evaluate the liver targeting property of ATC-Ⅱ-SLN. Compared to ATC-Ⅱ-SLN suspension. the liver AUC of p,o. ATC-Ⅱ-SLN was12.66fold higher and MRT was1.136fold longer. The results indicated that p.o. ATC-Ⅱ-SLN have good liver-targeting effect.Animals transplanted tumor experiment,4T-1mouse breast cancer cells were inoculated subcuta neously in BALB/c mice, in vivo tumor inhibition test to investigate the ATC-II-SLN and the ATC-II a dministration after the suppression ofsolid tumortumor rate. The results show that the ATC II-SLN stron ger tumor inhibitioncompared with the ATC-II, which is1.42times the original drug, considerable positi vedrug.The first time prepared to ATC-II-SLN with Compritol888the ATO as the carrier material,the the preparation process is simple and feasible, with good reproducibility, could increase drug solubility,improve the bioavailability of drug,and enhance the targeting of drug in liver.So it was expected to become a new drug delivery system of ATC-Ⅱ and had good application prospect.