Ethylcellulose nanoparticles with bimodal size distribution as precursors for the production of very small nanoparticles

A common technique for the preparation of polymeric nanoparticles (NPs) from preformed polymers is the emulsification solvent evaporation (ESE) method. However, the particle size of such carriers can typically not reduced below 100 nm. A bimodal distribution of particle size when applying ESE to the preparation of ethylcellulose (EC) NPs was intended to obtain very small particles in a size range below 50 nm. The proportion and size of the small particle fraction (SPF) depended on the surfactant as well as on the EC type and concentration. The preparation was conducted with different pharmaceutically relevant surfactants (polyoxyethylene (23) lauryl ether, sodium dodecyl sulfate, cetyltrimethylammonium bromide, polyvinyl alcohol and polysorbate 20) and all permitted obtaining very small NPs. After purification from excess surfactant by diafiltration and separation of the SPF by centrifugation, monodispersed particles with mean sizes between 20.6 +/- 2.3nm and 49.7 +/- 4.8nm could be isolated. The entrapment of a lipophilic model drug led to encapsulation rates between 34.0 +/- 2.4% and 78.2 +/- 12.6%, which were size and surfactant dependent. The preparation of polymeric NPs in a size below 50 nm by a simple centrifugation step holds promise for therapeutic applications where larger particles would be inefficient.