CHAPTER 3: Monolithic Devices for Sustained Delivery of Protein Therapeutics for Ocular Disease
Published:20 Oct 2021
T. M. Rodriguez, D. A. Bernards, and T. A. Desai, in Implantable Technologies: Peptides and Small Molecules Drug Delivery, ed. V. Srivastava, The Royal Society of Chemistry, 2021, pp. 54-75.
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The prevalence of many ocular diseases increases with age, and as average global life expectancy increases the burden of age-related and diabetes-related eye diseases follows. Current drug-delivery technologies for ocular diseases rely on two principal modalities: topical drops and intravitreal injections. Topical drops primarily treat front-of-eye disease as complex anatomical and physiological barriers often limit the success of therapies targeting the back of the eye, especially with respect to protein delivery. Intravitreal injections, on the other hand, deliver protein therapeutics directly to the vitreous. However, problems including the large size, poor permeation, and susceptibility of proteins and peptides to degradation leads to the therapeutic benefits of these strategies lasting only several weeks. Patient compliance with frequent drug administration remains a challenge for effective treatment of ocular disease, prompting next-generation drug-delivery systems to explore ways to deliver therapeutics for extended periods of time. First-generation non-biodegradable reservoir-based systems were robust, contained large reservoirs delivering small molecules, and could be removed from the eye if adverse effects occurred. Future approaches can improve these technologies by developing devices that deliver protein and peptides, degrade upon drug depletion, and decrease or eliminate complications associated with surgical procedures. This chapter will highlight recent advances in ocular drug-delivery devices in preclinical stages, clinical trials, and those approved by the United States Food and Drug Administration. We will also describe ocular diseases of interest, the current state of proteins and peptides for ocular therapeutics, and considerations for sustained delivery of protein and biologics.