DEVELOPMENT OF POSITIVELY CHARGED COLLOIDAL DRUG CARRIERS - CHITOSAN COATED POLYESTER NANOCAPSULES AND SUBMICRON-EMULSIONS

Positively charged colloidal drug carriers have shown interesting prop erties with respect to the negatively charged systems: they have impro ved stability in the presence of biological cations and their interact ion with negatively charged biological membranes is facilitated. In th e present work, a new approach in order to provide a positive charge t o colloidal systems, i.e., poly-epsilon-caprolactone (PECL) nanocapsul es 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 3(3) was used to investigate the influence of several factors (CS viscosity, PECL concentration and le cithin concentration) on the physicochemical properties of the systems . All the formulations displayed a particle size in the nanometer rang e (200-500 nm) and a high positive surface charge (from +30 up to +60 mV). The statistical analysis of these data (surface response methodol ogy) indicated that both size and surface charge of the nanocapsules a nd submicron emulsions, were significantly affected by all factors und er investigation, the CS viscosity being the most relevant factor. The CS coating of the nanocapsules was found to be efficient in preventin g their destabilization in the presence of Ca2+. Furthermore, the pres ence 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% i rrespective of the presence of CS in the preparation. As expected, the diazepam release rate from the nanocapsules and submicron emulsions o ccurred rapidly and it was slightly slowed down due to the CS coating. These results clearly demonstrated that coating nanocapsules and subm icron emulsion with CS increases their potential use as drug delivery systems.