title: Biodegradable nanoparticles for controlled subconjunctival delivery of latanoprost acid: in vitro and in vivo evaluation. Preliminary results.
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.
authors.affiliation: Eye Institute of Thrace, Alexandroupolis, Greece. thangiar@googlemail.com
authors.forename: Athanassios
authors.initials: A
authors.lastname: Giarmoukakis
authors.forename: Georgios
authors.initials: G
authors.lastname: Labiris
authors.forename: Haris
authors.initials: H
authors.lastname: Sideroudi
authors.forename: Zinovia
authors.initials: Z
authors.lastname: Tsimali
authors.forename: Nefeli
authors.initials: N
authors.lastname: Koutsospyrou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Avgoustakis
authors.forename: Vassilios
authors.initials: V
authors.lastname: Kozobolis
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003228:Conjunctiva / Q000187:drug effects*; D016503:Drug Delivery Systems; D004655:Emulsions; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits; D014065:Tonometry, Ocular
chemical_list: D000959:Antihypertensive Agents; D004655:Emulsions; D011461:Prostaglandins F, Synthetic; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D000077338:Latanoprost