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Sunitinib malate-loaded biodegradable microspheres for the prevention of corneal neovascularization in rats.
Yang, Jin; Luo, Lixia; Oh, Yumin; Meng, Tuo; Chai, Guihong; Xia, Shiyu; Emmert, David; Wang, Bing; Eberhart, Charles G; Lee, Seulki; Stark, Walter J; Ensign, Laura M; Hanes, Justin; Xu, Qingguo.
Afiliação
  • Yang J; Department of Ophthalmology, Myopia Key Laboratory of Health PR, Eye & ENT Hospital of Fudan University, Shanghai 200031, China; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Center for Nanomedicine at the Wilmer Eye
  • Luo L; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; State Key Laboratory of Ophthalmology, Zhongshan O
  • Oh Y; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Russell H. Morgan Department of Radiology and Radi
  • Meng T; Departments of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • Chai G; Departments of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.
  • Xia S; The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
  • Emmert D; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Wang B; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, Fujian Medical Univer
  • Eberhart CG; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Pathology, The Johns Hopkins Univers
  • Lee S; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Russell H. Morgan Department of Radiology and Radi
  • Stark WJ; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
  • Ensign LM; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineerin
  • Hanes J; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineerin
  • Xu Q; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; The Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Departments of Pharmaceutics, Virginia Commonwealt
J Control Release ; 327: 456-466, 2020 11 10.
Article em En | MEDLINE | ID: mdl-32822742
ABSTRACT
Corneal neovascularization (NV) predisposes patients to compromised corneal transparency and visional acuity. Sunitinib malate (Sunb-malate) targeting against multiple receptor tyrosine kinases, exerts potent antiangiogenesis. However, the rapid clearance of Sunb-malate eye drops administered through topical instillation limits its therapeutic efficacy and poses a challenge for potential patient compliance. Sunb-malate, the water-soluble form of sunitinib, was shown to have higher intraocular penetration through transscleral diffusion following subconjunctival (SCT) injection in comparison to its sunitinib free base formulation. However, it is difficult to load highly water-soluble drugs and achieve sustained drug release. We developed Sunb-malate loaded poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres (Sunb-malate MS) with a particle size of approximately 15 µm and a drug loading of 7 wt%. Sunb-malate MS sustained the drug release for 30 days under the in vitro infinite sink condition. Subconjunctival (SCT) injection of Sunb-malate MS provided a prolonged ocular drug retention and did not cause ocular toxicity at a dose of 150 µg of active agent. Sunb-malate MS following SCT injection more effectively suppressed the suture-induced corneal NV than either Sunb-malate free drug or the placebo MS. Local sustained release of Sunb-malate through the SCT injection of Sunb-malate MS mitigated the proliferation of vascular endothelial cells and the recruitment of mural cells into the cornea. Moreover, the gene upregulation of proangiogenic factors induced by the pathological process was greatly neutralized by SCT injection of Sunb-malate MS. Our findings provide a sustained release platform for local delivery of tyrosine kinase inhibitors to treat corneal NV.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neovascularização da Córnea Tipo de estudo: Clinical_trials Limite: Animals / Humans Idioma: En Revista: J Control Release Assunto da revista: FARMACOLOGIA Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neovascularização da Córnea Tipo de estudo: Clinical_trials Limite: Animals / Humans Idioma: En Revista: J Control Release Assunto da revista: FARMACOLOGIA Ano de publicação: 2020 Tipo de documento: Article