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-capr olactone (PECL) nanocapsules, were designed based on a strategy that c ombines 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 corne al epithelium was attempted. The cationic polyaminoacid PLL was direct ly adsorbed onto preformed PECL nanocapsules whereas the cationic poly saccharide CS was included in the nanocapsules formation medium. The C S and PLL coatings conferred to nanocapsules a high positive surface c harge, nevertheless, they did not modify the release profile of the mo del drug indomethacin from the colloidal system. In vivo studies showe d that the systems investigated (uncoated, PLL-coated and CS-coated na nocapsules) 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 o f enhancing the ocular penetration of indomethacin was substantially d ifferent: the CS coating increased twice, whereas the PLL coating fail ed to increase the ocular bioavailability of indomethacin when compare d to the uncoated particles. Therefore, it is not the positive surface charge but the specific nature of CS that is responsible for the part icularly enhanced uptake of the CS-coated nanocapsules. In addition, t he PLL-coated and CS-coated nanocapsules displayed a good ocular toler ance. To summarize, the CS-coated nanocapsules represent a useful appr oach for increasing the ocular bioavailability of drugs. (C) 1997 Else vier Science B.V.