Study On The Prepartion Of Hydroxyeamptomeeine-loaded MePEG-PLA Nanoparicles And Their Anti-tumor In Vitro

Objective To prepare hydroxyeamptotheeine-loaded MePEG-block-PLA copolymer nanoparticles(HCPT-MePEG-PLA-NPs). Assessed the characterization of NPs, investigated their release behavior and anti-tumor activity in vitro. MePEG-PLA-NPs had been suggested as supports for the drug to extend releasing and enhance the anti-tumor activity.Methods The content of HCPT was determined by HPLC. HCPT-MePEG-PLA-NPs was prepared with MePEG-PLA as the carrier material by emulsion/solvent evaporation method. We prepared HCPT-MePEG-PLA-NPs by orthogonal design based on the investigation of single factors including mean diameter and size distribution, entrapment efficiency, drug loading of nanoparticles etc. Transmission electron microscopy was observed by transmission electron microscopy. The particle size and Zata potential were determined by laser granularity equipment. Entrapment efficiency and drug loading was determined by ultracentrifugation. Release behavior in vitro of HCPT-MePEG-PLA-NPs was studied by dialysis bag method. The inhibitory effect against tumor cells and the changes of cells morphology were investigated by MTT staining method.Results The content of HPCT was determined successfully by HPLC, and there is a good linear relationship between0.2～16.0μg·mL-1(r=0.9997). HCPT-MePEG-PLA-NPs prepared by the optimum formulation of30mg MePEG-PLA, the concentration and volume of emulsifier was2.0%and3mL. The appearance of NPs is spherical; Their mean particle size was (100.13±0.56) nm; The PDI was (0.08±0.02); Zata potential was (2.31±0.381) mV; The entrapment efficiency(EE) and the drug loading(DL) was (61.40±1.65)%and was (0.41±0.02)%. NPs could retard drug release in pH7.4PBS solution which contains20%ethanol and effectively inhibit the growth of tumor cells in vitro.Conclusion HCPT-MePEG-PLA-NPs prepared by emulsion/solvent evaporation method had a smooth and spherical appearance with well-distributed particle size and high entrapment efficiency. NPs had obviously sustained release characteristics and significantly anti-tumor activity. This experiment will provide important practical and theoretic reference for the design, development and evaluation of sustained release preparation of anti-tumor drugs.