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Controlled release of corticosteroid with biodegradable nanoparticles for treating experimental autoimmune uveitis.
Luo, Lixia; Yang, Jin; Oh, Yumin; Hartsock, Matthew J; Xia, Shiyu; Kim, Yoo-Chun; Ding, Zheng; Meng, Tuo; Eberhart, Charles G; Ensign, Laura M; Thorne, Jennifer E; Stark, Walter J; Duh, Elia J; Xu, Qingguo; Hanes, Justin.
Affiliation
  • Luo L; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, PR China; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Center for Nanomedicine, Wilmer Eye Institute, The Johns
  • Yang J; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Department of Ophthalmology, Myopi
  • Oh Y; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Department of Radiology, The Johns
  • Hartsock MJ; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA.
  • Xia S; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
  • Kim YC; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA.
  • Ding Z; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21231, USA.
  • Meng T; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • Eberhart CG; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Department of Pathology, The Johns
  • Ensign LM; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Department of Chemical and Biomole
  • Thorne JE; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21231, USA.
  • Stark WJ; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA.
  • Duh EJ; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA.
  • Xu Q; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Department of Pharmaceutics, Virgi
  • Hanes J; Department of Ophthalmology, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Center for Nanomedicine, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, 400 North Broadway, Baltimore, MD 21231, USA; Department of Chemical and Biomole
J Control Release ; 296: 68-80, 2019 02 28.
Article de En | MEDLINE | ID: mdl-30660629
ABSTRACT
Noninfectious uveitis is a potentially blinding ocular condition that often requires treatment with corticosteroids to prevent inflammation-related ocular complications. Severe forms of uveitis such as panuveitis that affects the whole eye often require a combination of topical and either regional or systemic corticosteroid. Regional corticosteroids are currently delivered inside the eye by intravitreal injection (e.g. Ozurdex®, an intravitreal dexamethasone implant). Intravitreal injection is associated with rare but potentially serious side effects, including endophthalmitis, retinal and vitreous hemorrhage, and retinal detachment. Subconjunctival (SCT) injection is a less invasive option that is a common route used for post-surgical drug administration and treatment of infection and severe inflammation. However, it is the water soluble form of dexamethasone, dexamethasone sodium phosphate (DSP), that has been demonstrated to achieve high intraocular penetration with subconjunctival injection. It is difficult to load highly water soluble drugs, such as DSP, and achieve sustained drug release using conventional encapsulation methods. We found that use of carboxyl-terminated poly(lactic-co-glycolic acid) (PLGA) allowed encapsulation of DSP into biodegradable nanoparticles (NP) with relatively high drug content (6% w/w) if divalent zinc ions were used as an ionic "bridge" between the PLGA and DSP. DSP-Zn-NP had an average diameter of 210 nm, narrow particle size distribution (polydispersity index ~0.1), and near neutral surface charge (-9 mV). DSP-Zn-NP administered by SCT injection provided detectable DSP levels in both the anterior chamber and vitreous chamber of the eye for at least 3 weeks. In a rat model of experimental autoimmune uveitis (EAU), inflammation was significantly reduced in both the front and back of the eye in animals that received a single SCT injection of DSP-Zn-NP as compared to animals that received either aqueous DSP solution or phosphate buffered saline (PBS). DSP-Zn-NP efficacy was evidenced by a reduced clinical disease score, decreased expression of various inflammatory cytokines, and preserved retinal structure and function. Furthermore, SCT DSP-Zn-NP significantly reduced microglia cell density in the retina, a hallmark of EAU in rats. DSP-Zn-NP hold promise as a new strategy to treat noninfectious uveitis and potentially other ocular inflammatory disorders.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Maladies auto-immunes / Uvéite / Zinc / Dexaméthasone / Hormones corticosurrénaliennes / Nanoparticules Type d'étude: Prognostic_studies Limites: Animals Langue: En Journal: J Control Release Sujet du journal: FARMACOLOGIA Année: 2019 Type de document: Article
Texte intégral
Ajouter à My VHL
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XML
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Maladies auto-immunes / Uvéite / Zinc / Dexaméthasone / Hormones corticosurrénaliennes / Nanoparticules Type d'étude: Prognostic_studies Limites: Animals Langue: En Journal: J Control Release Sujet du journal: FARMACOLOGIA Année: 2019 Type de document: Article