Non-invasive evaluation of toxicity in vitreoretinal domain following insertion of sustained release methotrexate micro-implant

Manna, Soumyarwit; Faraj, Rafaela Q Caixeta; Riemann, Blanca; Rao, Marepalli B.; Nair, Vineeth; Riemann, Christopher D.; Augsburger, James J.; Corrêa, Zélia M.; Banerjee, Rupak

doi:10.1016/j.exer.2021.108505

Cited by 4 publications

(10 citation statements)

References 24 publications

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“…Histopathology Study: The details of the histopathological findings have been reported in the non-invasive study of toxicity and performance of the same micro-implant on the same rabbits, as used in this study [ 31 ]. Briefly, the issues identified in the histopathology analysis were associated with surgical procedures.…”

Section: Resultsmentioning

confidence: 99%

“…Surgery : The details of the surgery for this study are reported in our recent study [ 31 ] involving the non-invasive evaluation of safety and toxicity of the same micro-implant. Briefly, each animal was evaluated for the vital signs (heart rate, respiration rate, temperature) prior to surgery (PS) and verified to be within normal limits.…”

Section: Methodsmentioning

confidence: 99%

“…Our group developed a biodegradable intravitreal micro-implant platform that delivers a sustained therapeutic dose of MTX to the VR domain for several months [ 11 , 28 , 29 , 30 , 31 , 32 ]. Initially, a CS and PLA-based MTX intravitreal micro-implant device was developed that was able to maintain a sustained release of MTX between 0.2 and 2 µg/day in vitro for more than 50 days [ 29 ] and a therapeutic concentration of 0.1–1 µM MTX for ~30 days in vivo [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…The evaluated molecular weight of ester-terminated PLGA 5050 (PLA/PGA copolymer ratio in PLGA is 50:50) (Lactel Biodegradable Polymers, AL) with an inherent viscosity of 0.82 in hexafluoroisopropanol at 30 °C was Mw = 287,000 with a polydispersity index of 2.78 [ 32 ]. The safety and toxicity of this improved PLGA and CS-based MTX micro-implant were validated in normal rabbit eyes using non-invasive techniques such as ERG, US, slit-lamp biomicroscopy (SLB), fundoscopy and intraocular pressure (IOP) measurement for a period of approximately 2 months [ 31 ]. Non-invasive evaluation proved the micro-implant to be safe and well tolerated in rabbit eyes for the whole duration of the study.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, the scope of the pilot studies was limited due to the limited number of rabbits (n = 8). Subsequently, a recent study involving the improved PLGA-coated CS-MTX micro-implant was focused on non-invasive parameters only (ERG, US, SLB, fundoscopy and IOP) [ 31 ]. This study is novel because it presents findings on the invasive parameters, such as pharmacokinetics and toxicity evaluation of the PLGA-coated CS-MTX micro-implant, in thirty rabbit eyes.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics and Toxicity Evaluation of a PLGA and Chitosan-Based Micro-Implant for Sustained Release of Methotrexate in Rabbit Vitreous

et al. 2021

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The present research investigates the pharmacokinetics and toxicity of a chitosan (CS) and poly(lactic-co-glycolic) acid (PLGA)-based methotrexate (MTX) intravitreal micro-implant in normal rabbit eyes. PLGA and CS-based micro-implants containing 400 µg of MTX were surgically inserted in the vitreous of twenty-four New Zealand rabbits using minimally invasive procedures. The PLGA-coated CS-MTX micro-implant and the placebo micro-implant were inserted in the right eye and in the left eye, respectively, of each rabbit. The intravitreal MTX concentration was evaluated on Days 1, 3, 7, 14, 28 and 56. A therapeutic concentration of MTX (0.1–1.0 µM) in the rabbit vitreous was observed for 56 days. The release of MTX in the therapeutic release phase followed first-order kinetics. Histopathologic evaluation on Days 14, 28 and 56 of the enucleated eyes demonstrated no signs of toxicity or any anatomical irregularity in the vitreoretinal domain. Additionally, the micro-implants were stationary at the position of their implantation throughout the duration of the study. The PLGA-coated CS-MTX micro-implant can serve as a potential alternative to the current treatment modality of intravitreal MTX injections based on its performance, thereby avoiding associated complications and the treatment burden of multiple injections.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%