Pharmaceutical Research

, Volume 34, Issue 5, pp 1083–1092 | Cite as

Ocular safety of Intravitreal Clindamycin Hydrochloride Released by PLGA Implants

  • Gabriella M. Fernandes-CunhaEmail author
  • Silvia Ligório Fialho
  • Gisele Rodrigues da Silva
  • Armando Silva-Cunha
  • Min Zhao
  • Francine Behar-Cohen
Research Paper



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.


biocompatibility clindamycin intravitreal implant ocular toxoplasmosis PLGA toxicity 



Human retinal pigment epithelial cell line


Clindamycin hydrochloride


2-(4-amidinophenyl)-1H -indole-6-carboxamidine


Dulbecco’s modified eagle medium: nutrient mixture F-12




Fetal bovine serum


Fluorescein isothiocyanate


Ganglion cell layer


Human amniotic membrane


4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid


Hypoxanthine phosphoribosyltransferase


Ionized calcium binding adaptor molecule 1


Interleukin 1 beta


Interleukin 6


Inner nuclear layer


Inducible nitric oxide synthase


Propidium iodide


Human Müller cell line


Optical coherence tomography


Outer nuclear layer


Phosphate-buffered saline


Polymerase chain reaction


Poly(lactic-co-glycolic acid)


Peanut Agglutinin


Standard deviation


Tumor necrosis factor alpha


Terminal deoxynucleotidyl transferase dUTP nick end labeling


Vascular endothelial growth factor



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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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Gabriella M. Fernandes-Cunha
    • 1
    • 2
    • 3
    • 4
    Email author
  • Silvia Ligório Fialho
    • 5
  • Gisele Rodrigues da Silva
    • 2
    • 3
    • 4
    • 6
  • Armando Silva-Cunha
    • 1
  • Min Zhao
    • 2
    • 3
    • 4
  • Francine Behar-Cohen
    • 2
    • 3
    • 4
  1. 1.Faculty of PharmacyFederal University of Minas GeraisBelo HorizonteBrazil
  2. 2.INSERM UMRS 1138, Team 17, Centre de Recherche des CordeliersParisFrance
  3. 3.Pierre and Marie Curie UniversityParisFrance
  4. 4.Paris Descartes UniversityParisFrance
  5. 5.Pharmaceutical and Biotechnological Development, Ezequiel Dias FoundationBelo HorizonteBrazil
  6. 6.Faculty of PharmacyFederal University of São João Del ReiDivinópolisBrazil

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