Vibhuti Agrahari
Posters: J Clin Exp Ophthalmol
Vision threatening disorders such as age-related macular degeneration (wet-AMD), diabetic retinopathy (DR) and diabetic macular edema (DME) require frequent intravitreal injections of anti-VEGF antibodies or fragments thereof. Frequent intravitreral injections are associated with many complications such as secondary infections (endophthalmitis), retinal hemorrhage, retinal detachment and more importantly patient non-compliance. Therefore, development of sustained release formulation which can reduce the frequency of intravitreal injection is a better therapeutic option. The objective of this study is to evaluate tolerability and biocompatibility of novel PB copolymers based formulations including thermosensitive gel, nanoparticles (NPs) and a composite formulation comprising NPs dispersed in gel following topical instillation as well as single intravitreal injection in rabbits. In this study, NP preparation method was successfully optimized to improve entrapment efficiency (EE) and drug loading (DL) of model macromolecules such as IgGFab and Catalase. With this optimized method, a remarkably improved EE (~ 46% to 76%) and DL (~15% to 18%) have been observed. Results of in vitro studies depicted a nearly zero order release for significantly longer duration of time (~120 days) without showing any burst release effect. Moreover, in vitro biocompatibility assay exhibited negligible release of cytokines suggesting biocompatible nature of PB copolymers. Further, in vivo tolerability study was performed following topical instillation and intravitreal injection. Results of in vivo tolerability study exhibited excellent biocompatibility without any perceptible signs of inflammation or cataract. Results revealed that PB copolymer based formulation can be used as a platform for the treatment of posterior segment ocular diseases
Vision threatening disorders such as age-related macular degeneration (wet-AMD), diabetic retinopathy (DR) and diabetic macular edema (DME) require frequent intravitreal injections of anti-VEGF antibodies or fragments thereof. Frequent intravitreral injections are associated with many complications such as secondary infections (endophthalmitis), retinal hemorrhage, retinal detachment and more importantly patient non-compliance. Therefore, development of sustained release formulation which can reduce the frequency of intravitreal injection is a better therapeutic option. The objective of this study is to evaluate tolerability and biocompatibility of novel PB copolymers based formulations including thermosensitive gel, nanoparticles (NPs) and a composite formulation comprising NPs dispersed in gel following topical instillation as well as single intravitreal injection in rabbits. In this study, NP preparation method was successfully optimized to improve entrapment efficiency (EE) and drug loading (DL) of model macromolecules such as IgGFab and Catalase. With this optimized method, a remarkably improved EE (~ 46% to 76%) and DL (~15% to 18%) have been observed. Results of in vitro studies depicted a nearly zero order release for significantly longer duration of time (~120 days) without showing any burst release effect. Moreover, in vitro biocompatibility assay exhibited negligible release of cytokines suggesting biocompatible nature of PB copolymers. Further, in vivo tolerability study was performed following topical instillation and intravitreal injection. Results of in vivo tolerability study exhibited excellent biocompatibility without any perceptible signs of inflammation or cataract. Results revealed that PB copolymer based formulation can be used as a platform for the treatment of posterior segment ocular diseases
