| Objective To prepare Curcumin loaded Poly(ethylene glycol)-Poly(ε-caprolactone) Nanopaticles (CUR-PEG-PCL-NPs), investigate their pharmaceutical characters, release behavior and anti-HepG2cell activity in vitro, pharmacokinetics in vivo in rats, in order to achieve the sustained-release and long-acting used nanoparticles of PEG-PCL as a carrier of curcumin in vivo.Methods Use poly(ethylene glycol)-poly(s-caprolactone) as the carrier, poloxamer188as the surfactants, prepare curcumin loaded poly(ethylene glycol)-poly(ε-caprolactone) nanopaticles (CUR-PEG-PCL-NPs) by emulsion solvent evaporation. Based on the single factor experiment, the orthogonal design was adopted to optimized formulation and technology of the preparation of CUR-PEG-PCL-NPs. Morphology of CUR-PEG-PCL-NPs prepared by best technology were observed by transmission electronmicroscope. Mean particle size, PDI and Zeta potential were estimated by laser particle size analyzer. Entrapment efficiency and drug loading were investigated by the method of centrifugation and high-performance liquid chromatography (HPLC). The drug release behavior of CUR-PEG-PCL-NPs in pH5.8PBS with20%ethanol was studied by dialysis method. Selected SD rats as experimental animal, the pharmacokinetic parameters were calculated and the pharmacokinetic profiles were characterized by comparing the groups of CUR-Sol after intravenous injection of CUR-PEG-PCL-NPs. Plasma concentration of CUR-PEG-PCL-NPs was determined by HPLC, and pharmacokinetic parameters were calculated by3p97. Human HepG2cells were treated with CUR-PEG-PCL-NPs, the inhibition of cells were investigated by MTT cell viability assay.Results The morphology of CUR-PEG-PCL-NPs was spherical. The mean particle size, polydispersity index, Zeta potential, entrapment efficiency and drug loading were (102.8±2.69) nm,(0.118±0.03),(-0.293±0.110) mV,(84.36±1.19)%and (4.70±0.27)%, respectively. The in vitro release profiles of the CUR-PEG-PCL-NPs in pH5.8PBS with20%ethanol was expressed well by Weibull equation, that is lnln (1/1-Q)=0.72751nt-1.4395(R=0.9940), R=0.9978. The main pharmacokinetic parameters of CUR-PEG-PCL-NPs group and CUR-Sol group after veil injection in rats were as follows:T1/2α were (7.76±1.80) min and (4.33±0.65) min, T1/2β were (20.11±5.30) min and (207.20±12.17) min, AUC0→∞were (248.59±25.31) μg·min·mL-1and (583.06±64.22) μg·min·mL-1, CL were (0.081±0.008) mL·min-1and (0.035±0.004) mL·min-1, respectively. The results indicated that the CUR-PEG-PCL-NPs suspension eliminated slower and presented a prolonged release. In vitro anti-tumor activity results showed that HepG2cells was inhibited obviously by CUR-Sol and CUR-PEG-PCL-NPs, the CUR-PEG-PCL-NPs was better than CUR-Sol with the same concentration of CUR.Conclusion CUR-PEG-PCL-NPs prepared by emulsion solvent evaporation method was smooth and round with well-distributed particle size as well as high entrapment efficiency and drug loading. CUR-PEG-PCL-NPs showed the obvious sustained-release characteristic in vitro and in vivo, as well as the stronger antitumor activity in vitro compared with CUR-Sol. |
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