Ocular safety of Intravitreal Clindamycin Hydrochloride Released by PLGA Implants
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Drug ocular toxicity is a field that requires attention. Clindamycin has been injected intravitreally to treat ocular toxoplasmosis, the most common cause of eye posterior segment infection worldwide. However, little is known about the toxicity of clindamycin to ocular tissues. We have previously showed non intraocular toxicity in rabbit eyes of poly(lactic-co-glycolic acid) (PLGA) implants containing clindamycin hydrochloride (CLH) using only clinical macroscotopic observation. In this study, we investigated the in vivo biocompatibility of CLH-PLGA implants at microscotopic, cellular and molecular levels.
Morphology of ARPE-19 and MIO-M1 human retinal cell lines was examined after 72 h exposure to CLH-PLGA implant. Drug delivery system was also implanted in the vitreous of rat eyes, retinal morphology was evaluated in vivo and ex vivo. Morphology of photoreceptors and inflammation was assessed using immunofluorescence and real-time PCR.
After 72 h incubation with CLH-PLGA implant, ARPE-19 and MIO-M1 cells preserved the actin filament network and cell morphology. Rat retinas displayed normal lamination structure at 30 days after CLH-PLGA implantation. There was no apoptotic cell and no loss in neuron cells. Cones and rods maintained their normal structure. Microglia/macrophages remained inactive. CLH-PLGA implantation did not induce gene expression of cytokines (IL-1β, TNF-α, IL-6), VEGF, and iNOS at day 30.
These results demonstrated the safety of the implant and highlight this device as a therapeutic alternative for the treatment of ocular toxoplasmosis.
KEY WORDSbiocompatibility clindamycin intravitreal implant ocular toxoplasmosis PLGA toxicity
Human retinal pigment epithelial cell line
Dulbecco’s modified eagle medium: nutrient mixture F-12
Fetal bovine serum
Ganglion cell layer
Human amniotic membrane
Ionized calcium binding adaptor molecule 1
Interleukin 1 beta
Inner nuclear layer
Inducible nitric oxide synthase
Human Müller cell line
Optical coherence tomography
Outer nuclear layer
Polymerase chain reaction
Tumor necrosis factor alpha
Terminal deoxynucleotidyl transferase dUTP nick end labeling
Vascular endothelial growth factor
ACKNOWLEDGMENTS AND DISCLOSURES
The authors would like to acknowledge the financial support received from the following institutions: (Brazil), FAPEMIG (Minas Gerais – Brazil), Pró-reitoria de Pesquisa da Universidade Federal de Minas Gerais (Minas Gerais – Brazil), CAPES (Bolsistas da CAPES-Brasília/Brazil).
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