alexa Biodegradable nanoparticles for controlled subconjunctival delivery of latanoprost acid: in vitro and in vivo evaluation. Preliminary results.


Journal of Clinical & Experimental Ophthalmology

Author(s): Giarmoukakis A, Labiris G, Sideroudi H, Tsimali Z, Koutsospyrou N,

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Abstract Purpose of the study was to develop and assess a novel controlled drug delivery system of latanoprost acid (LA). Poly(lactide)/Monomethoxy-poly(ethyleneglycol) (PLA-PEG) nanoparticles (NPs) were prepared using an emulsification-solvent evaporation technique. NPs were characterized in vitro according to their size, ζ-potential, drug entrapment efficiency and LA release. LA-loaded NPs (equivalent to 8.5 μg LA) were administered into the subconjunctival space of normotensive rabbits (group A). A free LA solution of the same drug content was subconjunctivally injected in a second rabbit group (group B), while blank NPs were administered in a third group (group C). A group of untreated animals (group D) served as the control. Intraocular pressure (IOP) was monitored for 8 consecutive days, using the Tono-pen XL. Aqueous humor (AH) levels of LA were evaluated for 6 days post-administration, by means of HPLC. Mean nanoparticle size was 80 nm. The drug entrapment efficiency was 18.3\%. NPs sustained the release of LA over several days in vitro. Non-significant differences in baseline IOP were found between groups (p = 0.22). LA-loaded NPs exerted a significant hypotensive effect on group A, while IOP values remained significantly lower compared to the rest groups, throughout the study (p = 0.04). LA AH concentrations in group B continuously decreased with time, while LA levels in group A steadily increased. On day 6, LA levels were higher in group A compared to group B (344 ± 73.5 ng/ml and 228 ± 41.01 ng/ml, respectively). No adverse effects were observed. In conclusion, after subconjunctival administration, the LA-loaded NPs provided sustained LA delivery in vivo. They appear to be a promising system for the controlled subconjunctival delivery of LA. Copyright © 2013 Elsevier Ltd. All rights reserved. This article was published in Exp Eye Res and referenced in Journal of Clinical & Experimental Ophthalmology

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