The effect of a PEG versus a chitosan coating on the interaction of drug colloidal carriers with the ocular mucosa

The influence of the surface characteristics of colloidal drug carriers in their interaction with different biological surfaces is becoming increasingly evident. In order to investigate the importance of these characteristics in their interaction with the ocular mucosa, we developed three types of nanocapsules that differ in their surface properties: poly-epsilon-caprolactone (PECL) nanocapsules, chitosan (CS)-coated PECL nanocapsules and poly(ethylene glycol) (PEG)-coated PECL nanocapsules. Two different approaches were used to form these polymer coated nanocapsules: (i) the electrostatic anchorage of the coating onto the PECL nanocapsules-in the case of CS-and (ii) the use of the previously synthesized copolymer PECL-PEG for the formation of the nanocapsules. In both cases, the systems, prepared by the interfacial deposition technique, were loaded with a fluorescent dye (rhodamine) in order to quantify and visualize their interaction with the ocular surface ex vivo and in vivo. An important conclusion from the ex vivo studies is that the developed systems. and specially the CS-coated ones, enhanced the penetration of the encapsulated dye through the cornea. This effect was not simple due to the physical presence of the nanocapsules but to their ability to carry the encapsulated compound. The second conclusion from the confocal laser scanning microscopy (CLSM) studies is that the systems were able to enter the corneal epithelium by a transcellular pathway and that the penetration rate was dependent on the coating composition. The images suggest that the PEG coating accelerates the transport of the nanocapsules across the whole epithelium, whereas the CS coating favours the retention of the nanocapsules in the superficial layers of the epithelium. The specific behaviour of CS-coated systems was also corroborated in vivo. These results indicate that the surface composition of colloidal drug carriers affects their biodistribution in the eye. Therefore, this surface modification approach can be used as a targeting strategy in ocular drug delivery. (C) 2003 Elsevier B.V. All rights reserved.