Purpose. The aim of this study was to investigate whether biodegradable nanocapsules could be obtained by the emulsification-diffusion technique.

Methods. This technique consists of emulsifying an organic solution containing an oil, a polymer, and a drug in an aqueous solution of a stabilizing agent. The subsequent addition of water to the system induces solvent diffusion into the external phase, resulting in the formation of colloidal particles. Nanoparticles obtained in this way were characterized by their particle size, zeta potential, isopycnic density and drug entrapment. The shape, surface and structure of the nanocapsules were evaluated by freeze fracture scanning electron microscopy (SEM) and by atomic force microscopy (AFM).

Results. Density gradient centrifugation confirmed the formation of nanocapsules. The density was found to be intermediate between those of nanoemulsions and nanospheres. The existence of a unique density band indicated high yields. Nanocapsule density was a function of the original oil/polymer ratio, revealing that the polymer content and, consequently, the wall thickness, can be controlled by this method. SEM and AFM showed the presence of capsular structures with smooth homogeneous walls. The versatility and effectiveness of the method were demonstrated using different lipophilic drug/oil core/wall polymer/partially water-miscible solvent systems. The mechanism of nanocapsule formation was explained as a chemical instability (diffusion stranding) generated during diffusion.

Conclusions. This study demonstrated that the emulsification-diffusion technique enables the preparation of nanocapsules in a simple, efficient, reproducible and versatile manner.