title: Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats.
abstract: To study the suitability of injectable microspheres based on poly(ester amide) (PEA) or poly lactic-co-glycolic acid (PLGA) as potential vehicles for intravitreal drug delivery in rat eyes. Dexamethasone-loaded PEA microspheres (PEA + DEX) were also evaluated.
  
  
  
  Forty male Sprague Dawley rats were divided into four groups that received different intravitreally injected microspheres: PEA group (n = 12); PLGA group (n = 12); PEA + DEX group (n = 8); and control group (no injection, n = 8). Electroretinography (ERG), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (sdOCT) were performed at baseline, weeks 1 and 2, and months 1, 2, and 3 after intravitreal injection. Eyes were histologically examined using light microscopy and transmission electron microscopy at the end of the in vivo study.
  
  
  
  There were no statistically significant changes in ERG among the groups. Abnormal FAF pattern and abnormal deposits in OCT were observed after injection but almost completely disappeared between week 2 and month 3 in all injected groups. GFAP staining showed that Müller glia cell activation was most pronounced in PLGA-injected eyes. Increased cell death was not observed by TUNEL staining at month 1. In electron microscopy at month 3, the remnants of microparticles were found in the retinal cells of all injected groups, and loss of plasma membrane was seen in the PLGA group.
  
  
  
  Although morphological changes such as mild glial activation and material remnants were observed histologically 1 month and 3 months after injection in all injected groups, minor cell damage was noted only in the PLGA group at 3 months after injection. No evidence of functional abnormality relative to untreated eyes could be detected by ERG 3 months after injection in all groups. Changes observed in in vivo imaging such as OCT and FAF disappeared after 3 months in almost all cases.
authors.affiliation: Institute for Ophthalmic Research at the Centre for Ophthalmology, University of Tübingen, Germany. Electronic address: tobias.peters@uni-tuebingen.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Peters
authors.affiliation: Department of Ophthalmology, Korea University College of Medicine, Seoul, South Korea.
authors.forename: Seong-Woo
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Institute for Ophthalmic Research at the Centre for Ophthalmology, University of Tübingen, Germany.
authors.forename: Vinicius
authors.initials: V
authors.lastname: Castro
authors.affiliation: Institute for Ophthalmic Research at the Centre for Ophthalmology, University of Tübingen, Germany.
authors.forename: Krunoslav
authors.initials: K
authors.lastname: Stingl
authors.affiliation: Institute for Ophthalmic Research at the Centre for Ophthalmology, University of Tübingen, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Strasser
authors.affiliation: Institute for Ophthalmic Research at the Centre for Ophthalmology, University of Tübingen, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Bolz
authors.affiliation: Institute for Ophthalmic Research at the Centre for Ophthalmology, University of Tübingen, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schraermeyer
authors.affiliation: DSM, Urmonderbaan 22, Geleen, The Netherlands.
authors.forename: George
authors.initials: G
authors.lastname: Mihov
authors.affiliation: DSM, Urmonderbaan 22, Geleen, The Netherlands.
authors.forename: MengMeng
authors.initials: M
authors.lastname: Zong
authors.affiliation: Sanitary Research Institute of the San Carlos Clinical Hospital, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Andres-Guerrero
authors.affiliation: Sanitary Research Institute of the San Carlos Clinical Hospital, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Spain.
authors.forename: Rocio
authors.initials: R
authors.lastname: Herrero Vanrell
authors.affiliation: DSM, Urmonderbaan 22, Geleen, The Netherlands.
authors.forename: Aylvin A
authors.initials: AA
authors.lastname: Dias
authors.affiliation: Department of Chemistry, University of Durham, United Kingdom.
authors.forename: Neil R
authors.initials: NR
authors.lastname: Cameron
authors.affiliation: Institute for Ophthalmic Research at the Centre for Ophthalmology, University of Tübingen, Germany; Werner Reichardt Centre for Integrative Neuroscience (CIN) and Centre for Ophthalmology, University of Tübingen, Germany.
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
mesh_terms: D016115:Albinism, Oculocutaneous; D000577:Amides / Q000009:adverse effects / Q000737:chemistry*; D000818:Animals; D002214:Capsules / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D004058:Diffusion; D058449:Intravitreal Injections / Q000379:methods; D019344:Lactic Acid / Q000009:adverse effects / Q000737:chemistry*; D008297:Male; D008422:Materials Testing; D008863:Microspheres; D011091:Polyesters / Q000009:adverse effects / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000009:adverse effects / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000033:anatomy & histology* / Q000187:drug effects / Q000502:physiology*
chemical_list: D000577:Amides; D002214:Capsules; D011091:Polyesters; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone
keywords: Aliphatic dicarboxylic acids and aliphatic α-ω diols (PEA); Fundus auto-fluorescence; Immunohistochemistry; Invivo electroretinography; Invivo optical coherence tomography; Poly ester amide based on α-amino acids; Poly lactic-co-glycolic acid (PLGA); TUNEL stain; Transmission electron microscopy