In vivo toxicity evaluation of mannitol included in freezed dry PEA-III microparticles

    loading  Checking for direct PDF access through Ovid

Abstract

Purpose

To analyze short term toxicity of the mannitol included (3,375 μg; 0,225%) in an unilateral single intravitreal (ITV) injection (1.5μl) of freezed dry polyester amide (PEA) microparticles (“MPs”).

Methods

SD rats were divided into: G1: ITV Mannitol plus BSS; G2: ITV BSS; G3: Aged-matched control. Clinical examination and animal sacrifice were performed 24 hours, 3 and 7 days post-injection (PI). Tissue sections were processed for H&E and immunofluorescence with antibodies against GFAP, Iba-1 and MHC class II.

Results

No clinical signs of inflammation were observed at any time point of the study. H&E: The conjunctiva in G1 and G2 had an inflammatory infiltrate that peaked at 24 hours and decreased by day 3. On day 7, tissues looked as aged-matched control. In both groups, some inflammatory cells were found in the vitreous 24h and 3 days PI, the latter being more intense in G1. Immunostaining: the reactivity of astrocytes and Müller cells in G1 was higher than in G2 up to day 3. In day 7 PI, there was a mild and sectorial reaction of Müller cells in G1. Microglia in G1 and G2 showed morphological signs of activation 24h and 3 days PI, the reaction being stronger in G1. On day 7 PI: i) all microglia in G2 and the microglia in the outer retina in G1 looked like control; ii) the microglia in the inner retina showed signs of activation in G1. No MHC-II upregulation was found in either group.

Conclusion

Intravitreal injection of 1.5μL of mannitol (3,375 μg; 0,225%) induces changes in the glial cells of SD rat retina that should be taken into account in biocompatibility assays after intravitreal injections of mannitol freezed dry microparticles.

Related Topics

    loading  Loading Related Articles