Preparation and characterization of poly lactide-co-glycolide nanoparticles of SN-38.

SN-38 (7-ethyl-10-hydroxycamptothecin) is the active metabolite of irinotecan (CPT-11), which is 100-1000-fold more cytotoxic than irinotecan. Nonetheless, the extreme hydrophobicity of SN-38 has prevented its clinical use. SN-38 is poorly soluble in aqueous solutions, and it is practically insoluble in most physiologically compatible and pharmaceutically acceptable solvents. One way of improving the solubility and stability of SN-38 is to formulate the drug into nanoparticles. Incorporation of cytotoxic agents into nanoparticles has also shown increased toxicity. In this study, poly lactide-co-glycolide was used for the preparation of nanoparticles of SN-38. The nanoparticles were fabricated by an emulsification/solvent evaporation method. The effect of several variables on nanoparticle characteristics was evaluated, including the ratio of drug-polymer, the amount of the poly vinyl alcohol as surfactant, and the internal phase volume/composition. The SN-38 encapsulation efficiency and the particle size distribution were optimized by varying these parameters. Nanoparticles were spherical with a relatively mono-dispersed size distribution. As the ratio of acetone to dichloromethane increased, a considerable decrease in the particle size of nanoparticles was achieved. The encapsulation efficiency of all samples was more than 80%. Changing the poly vinyl alcohol concentration in the external phase had some effects on size and morphology and encapsulation efficiency. It was shown that SN-38 nanoparticles are considerably stable in a long-term stability study.