Purpose: Quantitative understanding of the transport of therapeutic macromolecules following intraocular injections is critical for the design of efficient strategies in treating eye diseases, such as neovascular (wet) age-related macular degeneration (AMD) and macular edema (ME). Antiangiogenic treatments, such as neutralizing antibodies against VEGF or recently characterized antiangiogenic peptides, have shown promise in slowing disease progression. Methods: We developed a comprehensive three-dimensional (3D) transport model for intraocular injections using published data on drug distribution in rabbit eyes following intravitreal and suprachoroidal (SC) injection of sodium fluorescein (SF), bevacizumab, and ranibizumab. The model then was applied to evaluate the distribution of small molecules and antiangiogenic proteins following intravitreal and SC injections in human eyes. Results: The model predicts that intravitreally administered molecules are substantially mixed within the vitreous following injection, and that the long-term behavior of the injected drug does not depend on the initial mixing. Ocular pharmacokinetics of different drugs is sensitive to different clearance mechanisms. Effective retinal drug delivery is impacted by RPE permeability. For VEGF antibody, intravitreal injection provides sustained delivery to the retina, whereas SC injection provides more efficient, but short-lived, retinal delivery for smaller-sized molecules. Long-term suppression of neovascularization through SC administration of antiangiogenic drugs necessitates frequent injection or sustained delivery, such as microparticle-based delivery of antiangiogenic peptides. Conclusions: A comprehensive 3D model for intravitreal and SC drug injection is developed to provide a framework and platform for testing drug delivery routes and sustained delivery devices for new and existing drugs.
Purpose: Quantitative understanding of the transport of therapeutic macromolecules following intraocular injections is critical for the design of efficient strategies in treating eye diseases, such as neovascular (wet) age-related macular degeneration (AMD) and macular edema (ME). Antiangiogenic treatments, such as neutralizing antibodies against VEGF or recently characterized antiangiogenic peptides, have shown promise in slowing disease progression. Methods: We developed a comprehensive three-dimensional (3D) transport model for intraocular injections using published data on drug distribution in rabbit eyes following intravitreal and suprachoroidal (SC) injection of sodium fluorescein (SF), bevacizumab, and ranibizumab. The model then was applied to evaluate the distribution of small molecules and antiangiogenic proteins following intravitreal and SC injections in human eyes. Results: The model predicts that intravitreally administered molecules are substantially mixed within the vitreous following injection, and that the long-term behavior of the injected drug does not depend on the initial mixing. Ocular pharmacokinetics of different drugs is sensitive to different clearance mechanisms. Effective retinal drug delivery is impacted by RPE permeability. For VEGF antibody, intravitreal injection provides sustained delivery to the retina, whereas SC injection provides more efficient, but short-lived, retinal delivery for smaller-sized molecules. Long-term suppression of neovascularization through SC administration of antiangiogenic drugs necessitates frequent injection or sustained delivery, such as microparticle-based delivery of antiangiogenic peptides. Conclusions: A comprehensive 3D model for intravitreal and SC drug injection is developed to provide a framework and platform for testing drug delivery routes and sustained delivery devices for new and existing drugs.
Authors: Raquel Lima E Silva; Yogita Kanan; Adam C Mirando; Jayoung Kim; Ron B Shmueli; Valeria E Lorenc; Seth D Fortmann; Jason Sciamanna; Niranjan B Pandey; Jordan J Green; Aleksander S Popel; Peter A Campochiaro Journal: Sci Transl Med Date: 2017-01-18 Impact factor: 17.956
Authors: Laurence A Hutton-Smith; Eamonn A Gaffney; Helen M Byrne; Philip K Maini; Kapil Gadkar; Norman A Mazer Journal: Mol Pharm Date: 2017-07-03 Impact factor: 4.939
Authors: K Ohno-Matsui; I Morita; J Tombran-Tink; D Mrazek; M Onodera; T Uetama; M Hayano; S I Murota; M Mochizuki Journal: J Cell Physiol Date: 2001-12 Impact factor: 6.384
Authors: Anita N Penkova; Shuqi Zhang; Mark S Humayun; Scott Fraser; Rex Moats; Satwindar Singh Sadhal Journal: J Porous Media Date: 2020 Impact factor: 1.663
Authors: Wenjing Xuan; Aji Alex Moothedathu; Tuo Meng; David C Gibson; Jinhua Zheng; Qingguo Xu Journal: Drug Discov Today Date: 2020-10-07 Impact factor: 7.851