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Study Of The Mechanism Of Interaction Of Poly(ϵ-caprolactone) Nanocapsules With The Cornea By Confocal Laser Scanning Microscopy

P. Calvo, C. Thomas, M. J. Alonso, J. L. Vila-jato, J. Robinson
Published 1994 · Chemistry

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Abstract With the aim of exploring the potential of poly(ϵ-caprolactone) (PECL) nanocapsules as drug carriers for ocular administration, the present study examined the mechanism of interaction of these nanocapsules with the corneal and conjunctival epithelia. In the first stage of this work, corneas were mounted in a perfusion cell, incubated with a suspension of rhodamine 6G-loaded PECL nanocapsules and subsequently observed by confocal laser scanning microscopy. Fluorescence signals were only observed within the epithelial cells, but not in the intercellular junctions, thus demonstrating the intracellular localization of the fluorescent nanocapsules. To determine whether this penetration could be associated with cellular lysis or endocytotic uptake, corneas were pretreated with blank nanocapsules and then stained with propidium iodide, a fluorescent dye which distinguishes viable from non-viable cells. Confocal images of the pretreated corneas did not display any fluorescence signal, thus indicating that PECL nanocapsules penetrate the corneal epithelial cells by an endocytotic mechanism. In the second stage of the work, rabbit corneas and conjunctivas were removed after in vivo instillation of the nanocapsule suspension and then analyzed by confocal laser scanning microscopy. The in vivo results corroborated the endocytosis uptake mechanism of nanocapsules by the cornea. On the other hand, no nanocapsules were observed in the conjunctival epithelium, which indicates a selective interaction of the PECL nanocapsules for the cornea vs the conjunctiva. These results suggest the ability of these colloidal carriers to specifically target drugs to the cornea while avoiding systemic drug loss through the conjunctiva. To summarize, PECL nanocapsules are shown to be the first demonstrated targeted corneal drug delivery system. Consequently, they may represent a useful approach to promote corneal penetration while simultaneously reducing conjunctival systemic absorption of drugs. This implies a potential increase in therapeutic effect and a reduction of systemic side effects.
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