Biodegradable chitosan and polylactic acid-based intraocular micro-implant for sustained release of methotrexate into vitreous: analysis of pharmacokinetics and toxicity in rabbit eyes.
Graefes Arch Clin Exp Ophthalmol
; 253(8): 1297-305, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-25896109
ABSTRACT
PURPOSE:
The purpose of this study was to evaluate the pharmacokinetics and toxicity of a chitosan (CS) and polylactic acid (PLA) based methotrexate (MTX) intravitreal micro-implant in an animal model using rabbit eyes.METHODS:
CS- and PLA-based micro-implants containing 400 µg of MTX were fabricated using lyophilization and dip-coating techniques. The micro-implants were surgically implanted in the vitreous of eight New Zealand rabbits employing minimally invasive technique. The PLA-coated CS-MTX micro-implant was inserted in the right eye and the placebo micro-implant in the left eye of each rabbit. Two rabbits were euthanized at each pre-determined time point post-implantation (days 5, 12, 19, and 33) for pharmacokinetics and histopathology evaluation.RESULTS:
A therapeutic concentration of MTX (0.1-1.0 µM) in the vitreous was detected in the rabbit eyes studied for 33 days. The MTX release from the coated micro-implants followed a first order kinetics (R (2) ~ 0.88), implying that MTX release depends on the concentration of MTX in the micro-implant. Histopathological analysis of the enucleated eyes failed to show any signs of infection or tissue toxicity in any of the specimens.CONCLUSION:
The PLA-coated CS-MTX micro-implants were able to deliver therapeutic release of MTX for a period of more than 1 month without detectable toxicity in a rabbit model. The micro-implants can be further investigated as a prospective alternative to current treatment protocols of repeated intravitreal MTX injections in intraocular disorders such as primary intraocular lymphoma, and selected cases of non-microbial intraocular inflammation.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Polímeros
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Corpo Vítreo
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Metotrexato
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Sistemas de Liberação de Medicamentos
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Ácido Láctico
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Implantes Absorvíveis
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Quitosana
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Antimetabólitos Antineoplásicos
Tipo de estudo:
Guideline
Limite:
Animals
Idioma:
En
Revista:
Graefes Arch Clin Exp Ophthalmol
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos