Abstract
Purpose: :
To evaluate the use of Pluronic F127 as a potential intravitreal drug delivery vehicle using a rabbit model, and to identify toxic effects on ocular tissues.
Methods: :
Ten adult New Zealand White adult rabbits were divided into 4 groups according to the concentration and volume of Pluronic used – Grp 1 (2 rabbits): 0.1ml of 30% solution; Grp 2 (3 rabbits): 0.05ml of 30%; Grp 4 (3 rabbits): 0.05ml of 20%; Grp 4 (2 rabbits) received 0.05ml of sodium choride 0.9% to serve as a control group. All animals received an intravitreal injection of Pluronic solution only in the right eye and the left eye served as a control eye. Outcome measures include clinical examination parameters, serial electroretinogram (ERG) and histologic examination. This study was approved by the Institutional Animal Care and Use Committee (IACUC).
Results: :
All rabbits had normal clinical examination and no significant inter–ocular difference in ERG responses at pre–injection. Regardless of the concentration and volume of Pluronic, eyes with intravitreal injection of Pluronic had severely reduced or undetectable ERG response by the 8th day after injection. No significant reduction of ERG response was detected in the uninjected control (left) eyes of these rabbits. The ERG responses of the injected and non–injected control eyes of Grp 4 saline control animals were very similar through out the study period. There was no clinical evidence of infection or inflammation but histologic examination revealed mild inflammatory infiltrate on the posterior vitreous hyaloid of injected eyes in Groups 1, 2 and 3. Pathologic changes were not detected in the retina or the optic nerve but some rabbits developed cataract, subluxed lens and raised intraocular pressure as a result of the injection.
Conclusions: :
The Pluronic F127 polymer hydrogel at the concentration of ≥20% is associated with severe retinal toxicity and thus it is not recommended to use as an intravitreal ocular drug delivery vehicle.
Keywords: drug toxicity/drug effects • electroretinography: non-clinical • microscopy: light/fluorescence/immunohistochemistry