Abstract
Positively charged colloidal drug carriers have shown interesting properties with respect to the negatively charged systems: they have improved stability in the presence of biological cations and their interaction with negatively charged biological membranes is facilitated. In the present work, a new approach in order to provide a positive charge to colloidal systems, i.e., poly-ɛ-caprolactone (PECL) nanocapsules and submicron emulsions, is presented. This is based on the coating of the colloidal droplets with the cationic polysaccharide chitosan (CS). An experimental factorial design 33 was used to investigate the influence of several factors (CS viscosity, PECL concentration and lecithin concentration) on the physicochemical properties of the systems. All the formulations displayed a particle size in the nanometer range (200–500 nm) and a high positive surface charge (from + 30 up to + 60 mV). The statistical analysis of these data (surface response methodology) indicated that both size and surface charge of the nanocapsules and submicron emulsions, were significantly affected by all factors under investigation, the CS viscosity being the most relevant factor. The CS coating of the nanocapsules was found to be efficient in preventing their destabilization in the presence of Ca2+ . Furthermore, the presence of CS permitted the adequate dispersion of the nanocapsules upon freeze-drying. Finally, using diazepam as model drug, it was observed that the encapsulation efficiency was, in all cases, higher than 90% irrespective of the presence of CS in the preparation. As expected, the diazepam release rate from the nanocapsules and submicron emulsions occurred rapidly and it was slightly slowed down due to the CS coating. These results clearly demonstrated that coating nanocapsules and submicron emulsion with CS increases their potential use as drug delivery systems.
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