Formation of poly(l,d-lactide) spheres with controlled size by direct dialysis

In this work, we show that simple dialysis of a poly(dl-lactic acid) (PLA) solution against water resulted in the spontaneous formation of PLA spheres. We observed initial formation of particles with irregular shape and large size, which then were disrupted into uniform and smooth nanospheres. Further, the formation process of PLA spheres was also investigated by dynamic light scattering technique (DLS) in situ. Based on these experimental results, it was proposed that the PLA spheres were formed in three steps: (1) aggregation - individual PLA chains got aggregated with each other in solution; (2) formation and disruption of PLA particles; (3) solidification of PLA spheres. In addition, 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. The ease with which these spheres could be fabricated and the ability to control the size of spheres should facilitate investigations of their scope for drug delivery.