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Editors Selection IGR 12-2
Surgical treatment: Drug-delivery implant
Comment by Malik Kahook on:
57435 Evaluation of an injectable thermosensitive hydrogel as drug delivery implant for ocular glaucoma surgery, Xi L; Wang T; Zhao F et al., PLoS ONE, 2014; 9: e100632
See also comment(s) by Tina Wong •Long-term drug delivery using polymeric depot reservoirs for the treatment of various ophthalmic diseases has been extensively studied. In this report, Xi and colleagues investigate the use of a thermosensitive hydrogel for controlled release of mitomycin C (MMC) both in vitro and in vivo. The effects of MMC (both with and without gel) in vitro and in vivo were predictable with cytotoxicity and prolonged survival of blebs in treated rabbits. The duration of bleb survival in both MMC and Gel+MMC were similar and in line with previous publications. The initial burst release of MMC from the hydrogel was significant (> 50%/24 hr) revealing that further work will be needed to enhance the delivery profile and to potentially expand this system as a platform technology. Creating long-term drug delivery systems for ophthalmic applications is difficult and this study illustrates some of the obstacles that are present when attempting to translate findings from in vitro to in vivo. One specific hurdle is scaling up production of product in a way that is feasible economically. The authors state the "simple preparation [of the gel] can avoid the denaturation of bioactive proteins and peptides that results at extreme conditions (e.g., heating, organic solvent, etc.)". Realistically, the same simple preparation methods used in small scale studies will not be feasible when attempting to increase batch manufacturing while adhering to good manufacturing practice (GMP) standards that are required by regulatory agencies.
A major hurdle is proving an advantage of a long-term depot over current methods of drug delivery that would justify a change in practice
Another major hurdle is proving an advantage of a long-term depot over current methods of drug delivery that would justify a change in practice. While this report illustrates a novel method for delivering MMC to the subconjunctival space in a rabbit model of glaucoma filtration surgery, the benefits over traditional MMC delivery methods are not clear. Further work by the authors may tease out specific advantages to their polymer system.
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