Abstract
Treatment options for retinal diseases, such as neovascular age-related macular degeneration, diabetic retinopathy, and retinal vascular disorders, have markedly expanded following the development of anti-vascular endothelial growth factor intravitreal injection methods. However, because intravitreal treatment requires monthly or bimonthly repeat injections to achieve optimal efficacy, recent investigations have focused on extended drug delivery systems to lengthen the treatment intervals in the long term. Dose escalation and increasing molecular weight of drugs, intravitreal implants and nanoparticles, hydrogels, combined systems, and port delivery systems are presently under preclinical and clinical investigations. In addition, less invasive techniques rather than intravitreal administration routes, such as topical, subconjunctival, suprachoroidal, subretinal, and trans-scleral, have been evaluated to reduce the treatment burden. Despite the latest advancements in the field of ophthalmic pharmacology, enhancing drug efficacy with high ocular bioavailability while avoiding systemic and local adverse effects is quite challenging. Consequently, despite the performance of numerous in vitro studies, only a few techniques have translated to clinical trials. This review discusses the recent developments in ocular drug delivery to the retina, the pharmacokinetics of intravitreal drugs, efforts to extend drug efficacy in the intraocular space, minimally invasive techniques for drug delivery to the retina, and future perspectives in this field.
Highlights
Retinal diseases, such as neovascular age-related macular degeneration (AMD), diabetic retinopathy, and retinal vascular disorders, are the leading causes of vision deterioration in most developed countries [1]
Current anti-VEGF drugs, including bevacizumab (Avastin; Genentech, Inc., San Francisco, CA, USA), ranibizumab (Lucentis; Genentech, Inc., San Francisco, CA, USA), and aflibercept (Eylea; Regeneron, Inc., Tarrytown, NY; and Bayer Healthcare Pharmaceuticals, Berlin, Germany) are manufactured as humanized monoclonal antibodies. According to their intraocular pharmacokinetic properties, these biologic drugs have relatively short half-lives, thereby requiring monthly or bi-monthly injections to maintain their efficacy in the intraocular space [7,8,9,10]
Anti-VEGF treatment is effective and beneficial for numerous retinal disorders, frequent intravitreal drug injections become a significant treatment burden to patients and the healthcare system owing to the overall cost and invasive technique utilized [11,12,13,14]
Summary
Retinal diseases, such as neovascular age-related macular degeneration (AMD), diabetic retinopathy, and retinal vascular disorders, are the leading causes of vision deterioration in most developed countries [1]. Current anti-VEGF drugs, including bevacizumab (Avastin; Genentech, Inc., San Francisco, CA, USA), ranibizumab (Lucentis; Genentech, Inc., San Francisco, CA, USA), and aflibercept (Eylea; Regeneron, Inc., Tarrytown, NY; and Bayer Healthcare Pharmaceuticals, Berlin, Germany) are manufactured as humanized monoclonal antibodies. According to their intraocular pharmacokinetic properties, these biologic drugs have relatively short half-lives, thereby requiring monthly or bi-monthly injections to maintain their efficacy in the intraocular space [7,8,9,10]. With the help of tissue engineering, hydrogels, micro- and nanoparticles, and several other
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