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Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells.
Hsueh, Henry T; Kim, Yoo-Chun; Pitha, Ian; Shin, Matthew D; Berlinicke, Cynthia A; Chou, Renee Ti; Kimball, Elizabeth; Schaub, Julie; Quillen, Sarah; Leo, Kirby T; Han, Hyounkoo; Xiao, Amy; Kim, Youngwook; Appell, Matthew; Rai, Usha; Kwon, HyeYoung; Kolodziejski, Patricia; Ogunnaike, Laolu; Anders, Nicole M; Hemingway, Avelina; Jefferys, Joan L; Date, Abhijit A; Eberhart, Charles; Johnson, Thomas V; Quigley, Harry A; Zack, Donald J; Hanes, Justin; Ensign, Laura M.
Afiliação
  • Hsueh HT; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Kim YC; Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Pitha I; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Shin MD; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Berlinicke CA; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Chou RT; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Kimball E; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Schaub J; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Quillen S; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Leo KT; Department of Computational Biology, Bioinformatics, and Genomics, Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD 20742, USA.
  • Han H; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Xiao A; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Kim Y; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Appell M; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Rai U; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Kwon H; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Kolodziejski P; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Ogunnaike L; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Anders NM; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Hemingway A; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Jefferys JL; Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Date AA; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Eberhart C; Department of Pharmacology and Molecular Sciences, Johns Hopkins University, Baltimore, MD 21287, USA.
  • Johnson TV; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Quigley HA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Zack DJ; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Hanes J; Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Ensign LM; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Pharmaceutics ; 13(5)2021 May 01.
Article em En | MEDLINE | ID: mdl-34062883
ABSTRACT
Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life.
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Texto completo: 1 Bases de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Pharmaceutics Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Tipo de estudo: Prognostic_studies / Risk_factors_studies Idioma: En Revista: Pharmaceutics Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos