title: Ocular safety of Intravitreal Clindamycin Hydrochloride Released by PLGA Implants.
abstract: 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.
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil. gabriellafcunha@gmail.com.|INSERM UMRS 1138, Team 17, Centre de Recherche des Cordeliers, 75006, Paris, France. gabriellafcunha@gmail.com.|Pierre and Marie Curie University, 75005, Paris, France. gabriellafcunha@gmail.com.|Paris Descartes University, 75006, Paris, France. gabriellafcunha@gmail.com.
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: Fernandes-Cunha
authors.affiliation: Pharmaceutical and Biotechnological Development, Ezequiel Dias Foundation, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Silvia Ligório
authors.initials: SL
authors.lastname: Fialho
authors.affiliation: INSERM UMRS 1138, Team 17, Centre de Recherche des Cordeliers, 75006, Paris, France.|Pierre and Marie Curie University, 75005, Paris, France.|Paris Descartes University, 75006, Paris, France.|Faculty of Pharmacy, Federal University of São João Del Rei, Divinópolis, Minas Gerais, Brazil.
authors.forename: Gisele Rodrigues
authors.initials: GR
authors.lastname: da Silva
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Armando
authors.initials: A
authors.lastname: Silva-Cunha
authors.affiliation: INSERM UMRS 1138, Team 17, Centre de Recherche des Cordeliers, 75006, Paris, France.|Pierre and Marie Curie University, 75005, Paris, France.|Paris Descartes University, 75006, Paris, France.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: INSERM UMRS 1138, Team 17, Centre de Recherche des Cordeliers, 75006, Paris, France.|Pierre and Marie Curie University, 75005, Paris, France.|Paris Descartes University, 75006, Paris, France.
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002460:Cell Line; D002981:Clindamycin / Q000008:administration & dosage* / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D063928:Ependymoglial Cells; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D058449:Intravitreal Injections / Q000379:methods; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019736:Prostheses and Implants; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002981:Clindamycin
keywords: PLGA; biocompatibility; clindamycin; intravitreal implant; ocular toxoplasmosis; toxicity