Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats

Tobias Peters, Seong Woo Kim, Vinicius Castro, Krunoslav Stingl, Torsten Strasser, Sylvia Bolz, Ulrich Schraermeyer, George Mihov, Meng Meng Zong, Vanessa Andres-Guerrero, Rocio Herrero-Vanrell, Aylvin Dias, Neil R. Cameron, Eberhart Zrenner

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Abstract

Purpose 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. Methods 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. Results 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. Conclusions 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.

Original languageEnglish
Pages (from-to)157-168
Number of pages12
JournalBiomaterials
Volume124
DOIs
Publication statusPublished - 1 Apr 2017
Externally publishedYes

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)
  • Transmission electron microscopy
  • TUNEL stain

Cite this

Peters, Tobias ; Kim, Seong Woo ; Castro, Vinicius ; Stingl, Krunoslav ; Strasser, Torsten ; Bolz, Sylvia ; Schraermeyer, Ulrich ; Mihov, George ; Zong, Meng Meng ; Andres-Guerrero, Vanessa ; Herrero-Vanrell, Rocio ; Dias, Aylvin ; Cameron, Neil R. ; Zrenner, Eberhart. / Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats. In: Biomaterials. 2017 ; Vol. 124. pp. 157-168.
@article{e08274c1dcd1410685ae023f0b90dc61,
title = "Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats",
abstract = "Purpose 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. Methods 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. Results 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 M{\"u}ller 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. Conclusions 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.",
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), Transmission electron microscopy, TUNEL stain",
author = "Tobias Peters and Kim, {Seong Woo} and Vinicius Castro and Krunoslav Stingl and Torsten Strasser and Sylvia Bolz and Ulrich Schraermeyer and George Mihov and Zong, {Meng Meng} and Vanessa Andres-Guerrero and Rocio Herrero-Vanrell and Aylvin Dias and Cameron, {Neil R.} and Eberhart Zrenner",
year = "2017",
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doi = "10.1016/j.biomaterials.2017.02.006",
language = "English",
volume = "124",
pages = "157--168",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier",

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Peters, T, Kim, SW, Castro, V, Stingl, K, Strasser, T, Bolz, S, Schraermeyer, U, Mihov, G, Zong, MM, Andres-Guerrero, V, Herrero-Vanrell, R, Dias, A, Cameron, NR & Zrenner, E 2017, 'Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats', Biomaterials, vol. 124, pp. 157-168. https://doi.org/10.1016/j.biomaterials.2017.02.006

Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats. / Peters, Tobias; Kim, Seong Woo; Castro, Vinicius; Stingl, Krunoslav; Strasser, Torsten; Bolz, Sylvia; Schraermeyer, Ulrich; Mihov, George; Zong, Meng Meng; Andres-Guerrero, Vanessa; Herrero-Vanrell, Rocio; Dias, Aylvin; Cameron, Neil R.; Zrenner, Eberhart.

In: Biomaterials, Vol. 124, 01.04.2017, p. 157-168.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats

AU - Peters, Tobias

AU - Kim, Seong Woo

AU - Castro, Vinicius

AU - Stingl, Krunoslav

AU - Strasser, Torsten

AU - Bolz, Sylvia

AU - Schraermeyer, Ulrich

AU - Mihov, George

AU - Zong, Meng Meng

AU - Andres-Guerrero, Vanessa

AU - Herrero-Vanrell, Rocio

AU - Dias, Aylvin

AU - Cameron, Neil R.

AU - Zrenner, Eberhart

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Purpose 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. Methods 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. Results 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. Conclusions 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.

AB - Purpose 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. Methods 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. Results 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. Conclusions 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.

KW - Aliphatic dicarboxylic acids and aliphatic α-ω diols (PEA)

KW - Fundus auto-fluorescence

KW - Immunohistochemistry

KW - Invivo electroretinography

KW - Invivo optical coherence tomography

KW - Poly ester amide based on α-amino acids

KW - Poly lactic-co-glycolic acid (PLGA)

KW - Transmission electron microscopy

KW - TUNEL stain

UR - http://www.scopus.com/inward/record.url?scp=85012069113&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2017.02.006

DO - 10.1016/j.biomaterials.2017.02.006

M3 - Article

VL - 124

SP - 157

EP - 168

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -