title: Development of a method to quantify clindamycin in vitreous humor of rabbits' eyes by UPLC-MS/MS: application to a comparative pharmacokinetic study and in vivo ocular biocompatibility evaluation.
abstract: Ocular toxoplasmosis may result in uveitis in the posterior segment of the eye, leading to severe visual complications. Clindamycin-loaded poly(lactide-co-glycolide) (PLGA) implants could be applied to treat the ocular toxoplasmosis. In this study, the pharmacokinetic profiles of the drug administrated by PLGA implants and by intravitreal injections in rabbits' eyes were evaluated. The implant released the drug for 6 weeks while the drug administrated by intravitreal injections remained in the vitreous cavity for 2 weeks. Compared to the injected drug, the implants containing clindamycin had higher values of area under the curve (AUC) (39.2 vs 716.7 ng week mL(-1)) and maximum vitreous concentration (Cmax) (8.7 vs 13.83 ng mL(-1)). The implants prolonged the delivery of clindamycin and increased the contact of the drug with the eyes' tissues. Moreover, the in vivo ocular biocompatibility of the clindamycin-loaded PLGA implants was evaluated regarding to the clinical examination of the eyes and the measurement of the intraocular pressure (IOP) during 6 weeks. The implantable devices caused no ocular inflammatory process and induced the increase of the IOP in the fourth week of the study. The IOP augmentation could be related to the maximum concentration of clindamycin released from the implants. In conclusion, the PLGA implants based on clindamycin may be a therapeutic alternative to treat ocular toxoplasmosis.
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil. Electronic address: gabriellafcunha@gmail.com.
authors.forename: Gabriella M
authors.initials: GM
authors.lastname: Fernandes-Cunha
authors.affiliation: Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Dayana Rubio
authors.initials: DR
authors.lastname: Gouvea
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Gustavo de Oliveira
authors.initials: Gde O
authors.lastname: Fulgêncio
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Cíntia M F
authors.initials: CM
authors.lastname: Rezende
authors.affiliation: School of Pharmacy, Federal University of São João Del Rei, Divinópolis, MG, 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, Pampulha, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Juliana M
authors.initials: JM
authors.lastname: Bretas
authors.affiliation: Ezequiel Dias Foundation, Belo Horizonte, MG, Brazil.
authors.forename: Sílvia Ligório
authors.initials: SL
authors.lastname: Fialho
authors.affiliation: Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Norberto Peporine
authors.initials: NP
authors.lastname: Lopes
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Av. Presidente Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Armando
authors.initials: A
authors.lastname: Silva-Cunha
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D002981:Clindamycin / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004343:Drug Implants; D005123:Eye / Q000737:chemistry / Q000187:drug effects; D058449:Intravitreal Injections; D008297:Male; D008422:Materials Testing / Q000379:methods*; D011817:Rabbits; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014822:Vitreous Body / Q000737:chemistry* / Q000187:drug effects
chemical_list: D004343:Drug Implants; D002981:Clindamycin
keywords: Biocompatibility; Clindamycin hydrochloride; Ocular toxoplasmosis; Pharmacokinetic; UPLC–MS/MS