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
AN - SCOPUS:85012069113
SN - 0142-9612
VL - 124
SP - 157
EP - 168
JO - Biomaterials
JF - Biomaterials
ER -