Abstract
Purpose :
Most polymer drug delivery systems induce ocular inflammation and have limited duration of drug release, especially when delivered episclerally. The purpose of this study was to evaluate the in vitro release, tolerability, ocular drug distribution, and pharmacodynamics of bromfenac and brinzolamide released from silicone matrix implants in the episcleral space.
Methods :
In vitro release in phosphate buffered saline (7.4 pH, 37C) of low dose (12 mm x 2 mm; 7.74 mg total drug) and high dose (20 mm x 2 mm; 12.18 mg total drug) silicone matrix implants (30% bromfenac or brinzolamide by weight) for 84 days was measured by HPLC. New Zealand White rabbits had either a blank silicone implant (n=2 eyes), or a low or high dose bromfenac or brinzolamide implant placed episclerally (n=8 eyes each). Ocular inflammatory scoring (modified Hackett-McDonald) and intraocular pressure (IOP) (TonoVet) were measured at 0, 1-7, 10,14, 21, and 28 days after implantation. Tissues were collected at either 7 or 28 days, and eyes were immediately frozen for drug analysis or fixed in Davidson's solution and processed for histopathology.
Results :
In vitro release of both bromfenac and brinzolamide revealed an initial burst of drug release followed by a steady sustained release, with an estimated 12-month release profile. Both high and low dose implants were very well tolerated with only mild conjunctival hyperemia that resolved by 7-10 days. Eyes with implants releasing bromfenac had lower inflammatory scores than those with brinzolamide or blank implants, however, the differences were not significant. Eyes with brinzolamide implants had significantly lower IOP (mean reduction of between -4.5+/-0.4 and -4.9+/-0.5 [SEM]) in a dose dependent manner than those with bromfenac or control on days 3-28 after implantation (P<0.03). Tissue drug levels were commensurate with dose of implant. Histopathology revealed focal mononuclear infiltrates around the implant site at day 7 and mild fibrosis at day 28, but no evidence of intraocular damage or toxicity.
Conclusions :
Episcleral silicone matrix implants that release bromfenac or brinzolamide were exremely well tolerated and provided sustained drug levels and therapeutic effect for greater than 28 days with an estimated duration of delivery of greater than 12 months.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.