Preparation Of Drug Loaded Nanoparticles With Controlled Size By Direct Dialysis

Dialysis method was developed to prepare polymer particles in recent years. Dialysis method is an acceptable simple and effective preparation method for surfactant-free particles, which is expected to apply in industrial production. However, a systematic and in-depth evaluation of the effects of dialysis conditions on properties of particles is still not available in literature.Polylactic acid (PLA) is under extensive research because of its unique and excellent biocompatibility and biodegradability, particularly in biomedical field. Epirubicin (EPI) is a broad-spectrum antitumor antibiotic drug. To reduce the amount of administration and side effects, EPI loaded nanoparticles were prepared by dialysis. This paper focused on controlling the size of PLA nanoparticles, formation mechanism of nanoparticles during preparation process, and properties of drug-loaded nanoparticles. The contents are summarized as follows:1. Particle size control: the size of the spheres could be well controlled by the preparation conditions such as the speed of dialysis, initial solvent, initial water content and polymer concentration and other parameters. The mechanism of size change was also studied.2. The formation process of PLA spheres was investigated by dynamic light scattering technique (DLS), scanning electron microscopy (SEM), fluorescence probe in situ. Based on these experimental results, it was proposed that the PLA spheres were formed in three steps: (1) complexing - individual PLA chains got complexed with each other in solution; (2) formation and disruption of PLA particles; (3) solidification of PLA spheres.3. Preparation and properties of EPI-loaded PLA nanoparticles: effects of dialysis process on drug content, encapsulation efficiency and drug loading process, in addition, thermal properties, drug distribution and drug release properties of drug-loaded nanoparticles were investigated in this thesis. The results showed that drug content and drug encapsulation ration were high, particle with spherical shape was formed, and the drug release rate could be well controlled with pH of solution, drug content and size of nanoparticles.