Abstract
AimTo assess the efficacy of a biodegradable, prednisolone acetate implant in a rabbit uveitis model.MethodsRandomized, controlled study of biodegradable microfilms preloaded with prednisolone acetate (PA) in a rabbit uveitis model. Experimental uveitis was induced by unilateral intravitreal injection of Mycobacterium tuberculosis H37Ra antigen (50 ug; 1 ug/uL) in preimmunized rabbits. PA-loaded poly[d,l-lactide-co-ε-caprolactone] (PLC) microfilms (n = 10) and blank microfilms (n = 6) were implanted subconjunctivally. An estimate of PA release in vivo was calculated from measured residual PA amounts in microfilms after the rabbits were sacrificed. The eyes were clinically monitored for ocular inflammation for 28 days. Histopathological examination of the enucleated eyes was performed at the end of the study period.Results In vitro studies revealed that sandwich PA-loaded microfilm formulations exhibited higher release kinetic compared to homogenous PA-loaded microfilms. The 60–40–60% microfilm released an average of 0.034 mg/day of PA over the period of 60 days in vitro; and we found that approximately 0.12 mg/day PA was released in vivo. Animals implanted with the PA-loaded microfilms exhibited significantly lowered median inflammatory scores when compared against the control group in this model for recurrent uveitis (P<0.001). The implants were clinically well tolerated by all the animals. Histology results showed no significant scarring or inflammation around the PA-loaded microfilms.ConclusionOur pilot study demonstrated that a subconjunctival PA-loaded implant is effective in suppressing inflammation in the rabbit model of uveitis, by providing therapeutic levels of PA that attenuated the inflammatory response even after a rechallenge. Longer term studies are now needed to establish the therapeutic potential of such a delivery system for treatment of ocular inflammation.
Highlights
Uveitis is an inflammatory disorder affecting the iris, ciliary body or choroid, which is a relatively common eye disorder, with an estimated incidence rate of 17 and 22.6 per 100,000 person years[1,2]
We have demonstrated in previous studies the anti-fibrotic and anti-inflammatory properties of a subconjunctivally implanted prednisolone acetate (PA)-preloaded microfilm in the rabbit model of subconjunctival scarring following glaucoma filtration surgery [6] and rat keratoplasty model[7]
All three formulations, regardless of single layer or tri-layer formulations showed an initial burst release followed by steady sustained release of PA
Summary
Uveitis is an inflammatory disorder affecting the iris, ciliary body or choroid, which is a relatively common eye disorder, with an estimated incidence rate of 17 and 22.6 per 100,000 person years[1,2]. In patients with posterior uveitis, topical steroids are often unable to control inflammation due to poor ocular penetration to the posterior segment. In these patients, intravitreal administration delivers the highest concentration of steroid and sustained release intravitreal implants can provide therapeutic drug levels for up to 6 months[4]. Intravitreal administration delivers the highest concentration of steroid and sustained release intravitreal implants can provide therapeutic drug levels for up to 6 months[4] The disadvantages of this route of administration are the increased risk of raised intraocular pressure, endophthalmitis and retinal detachment. Should these corticosteroidrelated complications such as raised intraocular pressure leading to glaucoma occur, removal of the steroid implant from the posterior segment would be difficult
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
