Purchase this article with an account.
R. Herrero-Vanrell, D. Barbosa-Alfaro, M. García-Gutierrez, I. Fernández-Bueno, I. Molina-Martínez, J. Pastor-Jimeno; Tolerance of Juxtascleral Administration of Sterilized Plga Microparticles Unloaded and Loaded With Dexamethasone. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5300.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Intraocular injections of Dexamethasone (Dx) are used in posterior segment diseases treatment. Frequent injections (poorly tolerated) are needed for successful therapy. Biodegradable microparticles loaded with Dx would allow long-term therapies diminishing the number of injections. Juxtascleral (sub-Tenon) injection of microparticles (MPs) resulted less invasive than intravitreal administration. The aim of the present work is to evaluate the tolerance of a posterior juxtascleral injection of sterilized PLGA MPs (unloaded-MPs) and loaded with Dx (Dx-MPs).
MPs were prepared by the solvent evaporation technique (O/W emulsion).The drug:polymer (R502) ratio was 2:10(w/w) for Dx-MPs. MPs were sterilized using 60Co as radiation source (25 kGy). MPs morphology and size distribution was evaluated. In vitro release of Dx from MPs (5mg) was quantified (HPLC) for 65 days (pH 7.4). PLGA MPs were injected in 14 female pigmented rabbits (2.5-3.5Kg). Animals were divided in two groups: juxtascleral administration of unloaded-MPs and Dx-MPs. Experiments were performed in compliance with the ARVO statement for the Use of Animals in Ophthalmic and Visual Research. External and anterior segment examination, inverted image ophthalmoscopy and aplanation tonometry were performed before and 24hrs, 1, 2 and 4 weeks after MPs administration.
MPs ranged from 20-53µm in size and were spherical in shape. The encapsulation efficiency was 82.66.0±4.2% for Dx-MPs. The drug was released in vitro up to 65 days. The release rate from 1st day to 17th was 1.22±0.09µgDx/mgMPs/day. From 21th day to 49th an almost constant release of 3.73±0.05µgDx/mgMPs/day was observed. MPs released amounts of 0.25±0.09µgDx/mgMPs/day until the end of the assay. After juxtascleral administration, animals presented conjunctival congestion at 24h (3/7) and 2 weeks (1/7) for unloaded-MPs and at 24h (6/7) and 1 week (3/7) for Dx-MPs. No adverse signs related to conjunctival discharge, conjunctival swelling, aqueous flare, light reflex, iris involvement, pannus, vitreous opacity, vascular congestion, vitreal and retinal haemorrhage, and retinal detachment were observed. IOP values at 4 weeks after injection were 19.29±5.50mmHg(unloaded-MPs) and 18.71±4.23mmHg(Dx-MPs).
Clinical observations showed that the MPs presented in this study are well tolerated after juxtascleral administration in rabbit eyes.
This PDF is available to Subscribers Only