Evaluation of a prednisolone acetate-loaded subconjunctival implant for the treatment of recurrent uveitis in a rabbit model.
OBJECTIVE
To assess the efficacy of a biodegradable, prednisolone acetate implant in a rabbit uveitis model.


METHODS
Randomized, 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.


CONCLUSIONS
Our 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.
Singapore National Eye Centre, Singapore, Singapore; Singapore Eye Research Institute, Singapore, Singapore.
Marcus
M
Ang
Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
Xuwen
X
Ng
Singapore National Eye Centre, Singapore, Singapore; Singapore Eye Research Institute, Singapore, Singapore.
Cheewai
C
Wong
Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
Peng
P
Yan
Singapore National Eye Centre, Singapore, Singapore; Singapore Eye Research Institute, Singapore, Singapore.
Soon-Phaik
SP
Chee
Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
Subbu S
SS
Venkatraman
Singapore National Eye Centre, Singapore, Singapore; Singapore Eye Research Institute, Singapore, Singapore; Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
Tina T
TT
Wong
D000818:Animals; D003228:Conjunctiva / Q000601:surgery*; D004333:Drug Administration Routes; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D019736:Prostheses and Implants; D011817:Rabbits; D014605:Uveitis / Q000188:drug therapy*
C009935:prednisolone acetate; D011239:Prednisolone