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 (R2 ~ 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.
Original language | English (US) |
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Pages (from-to) | 1297-1305 |
Number of pages | 9 |
Journal | Graefe's Archive for Clinical and Experimental Ophthalmology |
Volume | 253 |
Issue number | 8 |
DOIs | |
State | Published - Aug 1 2015 |
Externally published | Yes |
Keywords
- Animal model
- Chitosan
- Methotrexate
- Micro-implant
- Polylactic acid
- Sustained release
ASJC Scopus subject areas
- Ophthalmology
- Sensory Systems
- Cellular and Molecular Neuroscience