Controlled release technology for anti-angiogenesis treatment of posterior eye diseases: Current status and challenges

Long‐term therapeutic effect in nonhuman primate eye from a single injection of anti‐VEGF controlled release hydrogel

“…The aqueous pharmacokinetics of intravitreally injected bolus bevacizumab in monkey eye showed an exponential decay similar to the results in previous studies (Figure 4). 18,23 The aqueous elimination half-life calculated assuming first order elimination was 3.5 days, which is similar to the value calculated by Miyake et al (2.8 days). 16 The in vitro release kinetics and the in vivo rabbit eye pharmacokinetics of the present hydrogel has been described previously.…”

“…Controlled release device on the other hand offers a potentially simpler solution that can be translated to clinics in a shorter time because the antibody drug has already been proven effective and safe. Various types of devices, including micropumps, polymeric reservoirs, polymeric implants, polymeric particles, hydrogels, and hybrid systems, have been developed in recent years . However, despite the intense efforts in the past decade, only two implant devices have been evaluated in early phase clinical trials and the results were unsatisfactory .…”

“…To overcome these obstacles, intravitreal controlled release systems that aim to prolong the therapeutic duration of anti‐VEGF has been actively pursued over the past 10 years in both industry and academia. However, the following problems have been encountered: (a) the time for protein release is not long enough; (b) the depot fails to preserve the protein activity; (c) the delivery vehicles are not compatible with ocular tissues . The lack of an animal model to evaluate the prolong therapeutic duration of these formulations brings an additional barrier to the translation of these devices to clinical use …”

“…(a) the time for protein release is not long enough; (b) the depot fails to preserve the protein activity; (c) the delivery vehicles are not compatible with ocular tissues. [16][17][18][19][20] The lack of an animal model to evaluate the prolong therapeutic duration of these formulations brings an additional barrier to the translation of these devices to clinical use. 18 Previously, we developed an injectable hydrogel composed of hyaluronic acid grafted with vinylsulfone (HA-VS) and dextran grafted with thiol (Dex-SH).…”

“…[16][17][18][19][20] The lack of an animal model to evaluate the prolong therapeutic duration of these formulations brings an additional barrier to the translation of these devices to clinical use. 18 Previously, we developed an injectable hydrogel composed of hyaluronic acid grafted with vinylsulfone (HA-VS) and dextran grafted with thiol (Dex-SH). Using the Blob model as a guidance for rational design, we were able to identify formulations that released bevacizumab in vivo in rabbit eyes for over 6 months with excellent biocompatibility.…”