Evaluation of cationic polymer-coated nanocapsules as ocular drug carriers

New colloidal systems for ocular application were developed and their capacity for increasing the corneal penetration of drugs investigated. Chitosan (CS)-coated and poly-L-lysine (PLL)-coated poly-epsilon-caprolactone (PECL) nanocapsules, were designed based on a strategy that combines the features of PECL nanocapsules as ocular carriers with the advantages of a cationic mucoadhesive coating. Using this approach, an improved interaction of the carrier with the negatively charged corneal epithelium was attempted. The cationic polyaminoacid PLL was directly adsorbed onto preformed PECL nanocapsules whereas the cationic polysaccharide CS was included in the nanocapsules formation medium. The CS and PLL coatings conferred to nanocapsules a high positive surface charge, nevertheless, they did not modify the release profile of the model drug indomethacin from the colloidal system. In vivo studies showed that the systems investigated (uncoated, PLL-coated and CS-coated nanocapsules) increased significantly the concentration of indomethacin in the cornea and aqueous humor with respect of a commercial eye drops. Nevertheless, the ability of PLL-coated and CS-coated nanocapsules of enhancing the ocular penetration of indomethacin was substantially different: the CS coating increased twice, whereas the PLL coating failed to increase the ocular bioavailability of indomethacin when compared to the uncoated particles. Therefore, it is not the positive surface charge but the specific nature of CS that is responsible for the particularly enhanced uptake of the CS-coated nanocapsules. In addition, the PLL-coated and CS-coated nanocapsules displayed a good ocular tolerance. To summarize, the CS-coated nanocapsules represent a useful approach for increasing the ocular bioavailability of drugs. (C) 1997 Elsevier Science B.V.