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The antibody bevacizumab (Avastin) has been used clinically to treat intraocular neovascular diseases based on its antivascular endothelial growth factor (VEGF) character. The anti-VEGF strategy for retinal neovascular diseases is limited by the short half-life of bevacizumab and thus requires frequent injections. This Article reports the sustained release of bevacizumab from a biocompatible material that is composed of a triblock copolymer of poly(2-ethyl-2-oxazoline)-b-poly(ε-caprolactone)-b-poly(2-ethyl-2-oxazoline) (PEOz-PCL-PEOz). The amphiphilic PEOz-PCL-PEOz triblock copolymer was synthesized in three steps. First, the PEOz was polymerized by methyl p-toluenesulfonate and 2-ethyl-2-oxazoline (EOz), and the living end was terminated by potassium hydroxide methanolic solution. Subsequently, the hydroxyl-PEOz was used as a macroinitiator for the ring-opening polymerization of ε-caprolactone using a Tin(II) octoate catalyst to synthesize the telechelic hydroxylated PEOz-PCL. Finally, the PEOz-PCL-PEOz triblock copolymer was obtained using the 1,6-hexamethylene diisocyanateas a coupling reagent. The PEOz-PCL-PEOz was chemically and molecularly characterized by GPC, (1)H NMR, and FTIR, and its aqueous solution (ECE hydrogel) showed a reversible sol (room temperature)-gel (physiological temperature) phase transition, which serves as an easy antibody-packing system with extended release. The biodegradability of ECE hydrogel was assessed by the porosity formation at different periods by scanning electron microscopy. The ECE hydrogel had no in vitro cytotoxicity on the human retinal pigment epithelial cell line by flow cytometry. The histomorphology and electrophysiology of the rabbit neuroretina were preserved after 2 months of intravitreal injection. In conclusion, the ECE hydrogel has a temperature-sensitive sol-gel phase transition and is effective in vitro. Its intraocular biocompatibility demonstrated its great potential to be widely used in biomedical applications for extended drug release.

Retinal transplantation aims to restore vision for patients suffering from retinitis pigmentosa and age-related macular degeneration. Because the retinal sheets are fragile in nature, it is difficult to maintain graft integrity during surgical manipulation and after transplantation. In the present work, we report the feasibility of applying sandwich-like gelatin membranes as encapsulating carriers for retinal sheet transplantation applications. The relationship between the Bloom index of gelatin and the functionality of carrier membranes was studied by determinations of mechanical property, dissolution degree, melting point, cytocompatibility, biocompatibility, and transplant transfer and encapsulation efficiency. Irrespective of their Bloom strength, the gelatin membranes had a thickness sufficient to provide mechanical support for retinal sheets and would be beneficial to overcome the fragility of transplants during intraocular delivery. It was found that the lower the Bloom value of gelatin, the lower melting point of membranes. This allowed for easy fabrication of a stable sandwich-like encapsulating structure at 37 degrees C. The gelatins with lower Bloom strengths could possibly be dissolved to an extent required for the establishment of close contact between the retinal grafts and defective tissues. In addition, the carrier membranes made from the gelatins with low Bloom values showed a relatively higher cytocompatibility and biocompatibility as well as a higher transfer and encapsulation efficiency as compared to those with high Bloom values. It is concluded that the effect of Bloom index of gelatin plays a significant role in the membrane functionality and the gelatins with low Bloom values have substantial potential to be further developed as effective encapsulating carriers for the intraocular delivery of retinal sheets.