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Kevin W. Burton, Cara Davis, Charles Hagemeier, Adrian Raiche, Jason Campbell, Brandon Smith, Jay Stone, Tony Anderson; Degradation Of Poly(lactide-co-glycolide) Microspheres In Vitro And In The Vitreous Of Rabbits. Invest. Ophthalmol. Vis. Sci. 2011;52(14):463.
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© ARVO (1962-2015); The Authors (2016-present)
Bioresorbable microparticles provide a promising platform for sustained delivery of therapeutics to the eye. The degradation of various PLGA polymers formulated into microspheres was compared in three different buffers in vitro and in the vitreous of New Zealand white rabbits. The rabbit study also collected basic ocular safety data over the six month study.
Placebo microsphere formulations consisting of poly(DL-lactide-co-glycolide) were prepared by the solvent extraction method. Variables tested included monomer ratios, molecular weight, and end groups. Polymer degradation, as determined by changes in molecular weight, was followed both in vivo in the rabbit vitreous and in vitro with various buffer media. Additional rabbit safety data collection included ocular observations, intraocular pressures, fundus photography, and histopathology.
Polymer degradation was slightly faster in vivo than in vitro. Molecular weight plateaued after 60 days in vivo. Higher molecular weight and a higher ratio of lactide to glycolide provided longer duration. There were no significant differences in the degradation rates of the polymers in buffer media at low versus high pH (pH=3.0 versus pH=7.4) or with the addition of surfactant. All microspheres were essentially absent at the six month termination of the in vivo study. Good ocular tolerability was seen with all polymers. Histopathology revealed only mild fibrosis in the areas where microparticles had been injected.
In vitro, polymer degradation is hypothesized to be due to an internally driven autocatalytic process. Even lower pH media did not significantly influence the rate of polymer MW change. Ocular tolerability and histopathology demonstrated a good overall profile in accordance with previous studies.
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