Design and Synthesis of Injectable Composite Hydrogel Containing Bevacizumab with or without Triamcinolone acetonide for the Treatment of Choroidal Neovascularization
Firouze Hatami1 *, Mozhgan Rezaei Kanavi1 , Hamid Ahmadieh2 , Sina Khosravi Mirzaei1 , Sare Safi3 , Mohammad Abolhosseini1 , Mohammad-reza Nabid4 , Ramin Nourinia5 , Sarvenaz Pakian4
- Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Ophthalmic Epidemiology Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Department of Polymer and Materials Chemistry, Faculty of Chemistry & Petroleum Sciences, Shahid Beheshti University, Tehran, Iran.
- Ophthalmic Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abstract: Intravitreal injection of hydrogel drug delivery system (DDS) sustained with anti-VEGF like Bevacizumab (Bev) could enable extended release of anti-VEGF to inhibit vascular proliferation and attenuate choroidal neovascularization (CNV). The major purpose of this study is to evaluate safety and efficacy of injectable carboxymethyl cellulose based hydrogels sustained with different doses of Bev with or without Triamcinolone (Tr) on rat models of laser-induced CNV
Methods: Intravitreal injection of fiber-embedded and Schiff base-crosslinked injectable hydrogel composite (Bev/Tr@FSHC) sustained with different doses of Bev (0.25mg/200µl or 0.1mg/200µl) with or without Tr (0.4mg/200µl), and of hydrogels without active drug (2µl) were performed. Hydrogel-free Bev with above-mention doses with or without Tr (0.4mg/200µl) and PBS were applied intravitreally in control groups. The safety of intravitreal hydrogel DDS was investigated by electroretinogram and histopathology (TUNEL test and immunohistochemistry for glial fibrillary acidic protein (GFAP)). Efficacy of intravitreal hydrogel DDS was evaluated in laser induced rat models of CNV via isolectin-B4 staining of choroidal-scleral flat mounts. Mean areas of CNV were calculated using ImageJ software, and then compared between the groups.
Results: Intravitreal injection of hydrogels DDS was proved to be safe based on ERG, TUNEL test and GFAP immune reactivity. Mean CNV area in intravitreal injection of hydrogel sustained with either of Bev (0.1 mg/200µl and 0.25mg/200µl) plus Tr (0.4mg/200µl) was significantly smaller than those of corresponding hydrogel-free controls (21256±9624µm2 vs. 28207±8699µm2 in 0.1mg/200µl Bev, P= 0.002; 20154±7913µm2 vs. 24622±9547µm2 in 0.25mg/200µl Bev, P=0.001).
Conclusion: Combined Intravitreal Bev and Tr loaded in hydrogels DDS, as compared to hydrogel-free intravitreal injection of combined Bev and Tr, significantly attenuated CNV areas in rat models of laser-induced CNV. Further study should be performed to investigate the persistence of the hydrogel-loaded drugs in the vitreous.
