Evaluation of a Prednisolone Acetate-Loaded Subconjunctival Implant for the Treatment of Recurrent Uveitis in a Rabbit Model

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.

Long‐Term Subconjunctival Delivery of Brimonidine Tartrate for Glaucoma Treatment Using a Microspheres/Carrier System

“…In this approach, the BT‐loaded M/CS may be implanted in the subconjunctiva, and may be periodically replaced when the BT release is complete (Figure S1, Supporting Information). Subconjunctival implants have been previously used to deliver drugs for conditions such as uveitis and glaucoma for extended periods of up to 1 month without damage to surrounding tissue . Biodegradable polymer films have also been implanted in the subconjunctiva for up to 6 months without surrounding tissue damage or inflammation, confirming the safety of the subconjunctival location for long‐term implantation.…”

A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model

“…16 We further loaded the PLC microfilms with prednisolone acetate (PA) and demonstrated that the PA microfilms significantly reduced corneal graft rejection after corneal transplantation, 17 reduced postoperative inflammation and prolonged bleb survival following glaucoma filtering surgery, 18 and suppressed the severity of uveitis in animal models. 19 We have also loaded the PLC microfilms with timolol maleate and demonstrated the sustained intraocular pressurelowering effects. 20 In the present study, we aimed to evaluate the efficacy of the biodegradable, tacrolimus-loaded PLC drug delivery system on allergic conjunctivitis using a mouse model.…”

Corticosteroids and Anti-Complement Therapy in Retinal Diseases

“…Ang (2014) has developed prednisolone acetate-loaded PCL microfilms to be implanted subconjunctivally for uveitis treatment and has reported that the formulation was effective in a rabbit uveitis model (Ang 2014). Wong (1989) published a patent (US 7846468) for immunosuppressive biodegradable ocular implants using PLGA and HPMC against transplant rejection.…”