IMPROVED OCULAR BIOAVAILABILITY OF INDOMETHACIN BY NOVEL OCULAR DRUG CARRIERS

The ability of different drug carriers to improve the ocular bioavaila bility of drugs was investigated in the rabbit eye. The assayed drug c arriers were suspensions of nanoparticles, nanocapsules and microparti cles made of poly-epsilon-caprolactone (PECL) and a submicron emulsion . Results indicated that the three submicron systems, nanoparticles, n anocapsules and emulsion, increased more than 3-fold the indomethacin concentration in the cornea, aqueous humour and iris-ciliary body at 0 .5 and 1 h post-instillation. Furthermore, an increased indomethacin o cular bioavailability of 300% was observed after instillation of the s ubmicron systems in comparison with the value obtained for a commercia l solution. In contrast, the microparticles hardly increased the ocula r bioavailability of indomethacin. The mechanism of interaction of the colloidal carriers with the corneal epithelium was investigated by co nfocal laser scanning microscopy. Confocal images indicated that submi cron particles penetrate into the corneal epithelium cells by an endoc ytic mechanism. The similar behaviour of the three colloidal carriers suggests that any of their specific ingredients (PECL, lecithin and oi l) acts as a penetration enhancer or an endocytotic stimulator. On the other hand, the favourable ocular penetration of indomethacin when en capsulated in the colloidal carriers, but not in the microparticles, l ed us to assume that the colloidal nature of these carriers is the mai n factor responsible for the increased ocular bioavailability of indom ethacin. PECL nanoparticles and nanocapsules as well as submicron emul sions are shown to be novel corneal drug carriers, thus representing a useful approach for increasing the ocular bioavailability of drugs.